Suchergebnisse

"Thèse en cotutelle : Université Laval, Québec, Canada, Philosophiæ doctor (Ph. D.) et Aix-Marseille Université, Marseille, France" ; Ravagée par la guerre et occupée pendant plusieurs années, la France a été le théâtre de changements majeurs dans la manière dont ses dirigeants ont appréhendé son avenir au sein du Concert des Nations. Ces derniers étaient conscients de l'importance qu'a eue l'empire entre 1940 et 1945 et le rôle central qu'il avait pour le rétablissement de la légitimité du pays en tant que Puissance mondiale. Dans le domaine économique, les colonies étaient conçues comme un apport essentiel au relèvement de la France et pour sa prospérité. Les décideurs français ont ainsi consolidé les liens entre la métropole française et ses colonies pour fonder une politique impériale sur les principes du républicanisme selon lesquels la République était « une et indivisible ». Les hommes politiques français ont raffermi l'emprise de la France sur leurs territoires d'outre-mer par la création de l'Union française et ont donné un second souffle à la constitution d'un État-Empire, un projet entamé dans les années 1930. La dernière phase d'expansion de l'empire du dix-neuvième siècle faisait place alors depuis les années 1920 et 1930 à une logique de développement et de mise en branle des projets coloniaux de manière à créer un empire qui pouvait constituer un ensemble cohérent. La poursuite de cette logique du mythe colonial français après 1945 a eu pour effet de modifier l'identité de la France en tant qu'acteur du système international. La France n'était plus perçue par ses agents sub-étatiques comme un simple État possédant des colonies, mais bien comme une nouvelle entité dans laquelle ses excroissances dans l'outre-mer faisaient dorénavant partie intégrante de l'État et contribuaient à forger un avenir, qui était dès lors inextricablement partagé. Le bien-fondé de la mission civilisatrice de la France se traduisait dans cette période par un sentiment de devoir envers les territoires d'outre-mer ; le devoir de les amener au développement économique moderne et à un stade civilisationnel supérieur. Ces mêmes convictions ont conduit les gouvernements français à envisager une autre issue à cette relation que celle de l'indépendance totale, encouragée par les mouvements de décolonisation. Cette nouvelle identité a des effets tangibles sur la conception et l'engagement des décideurs et les haut-fonctionnaires français dans les projets destinés à rapprocher les économies européennes et dans la poursuite de l'intégration européenne. Dans le cas de la CECA, puisque cette institution sectorielle avait peu d'impacts sur la production d'outre-mer, on envisageait les bénéfices à une association entre les continents européen et africain comme marginaux. Cependant, le facteur colonial devenait de plus en plus influent dans les prises de décisions effectuées par les haut-fonctionnaires et analystes français du ministère des Affaires étrangères. Il a d'ailleurs constitué l'un des points d'achoppement dans les négociations de la mise en place d'une armée européenne, car l'article 38 du Traité instituant la CED ne prévoyait pas de mesures permettant à la France de conserver les moyens de poursuivre ses opérations de pacification dans l'empire ainsi que la guerre d'Indochine. C'est en ce sens qu'après l'échec de la CED le gouvernement français sous le leadership d'Edgar Faure a entrepris de mener des réformes de manière à trouver une solution durable au dilemme de la vocation européenne ou mondiale de la France. Des réformes politiques et économiques majeures étaient envisagées afin de transformer l'Union française en une association fédérale franco-africaine librement consentie. L'ensemble français ne pouvait donc plus être intégré partiellement à des initiatives européennes, car cela contreviendrait aux principes républicains renforcés par les réformes. Dans le contexte de la « relance européenne », le gouvernement sous Guy Mollet proposait de lier le marché commun européen aux territoires d'outre-mer, ce qui aurait permis l'ouverture des marchés africains aux échanges européens. Intégrées dans cette Eurafrique, les colonies auraient ainsi vu les bénéfices de conserver le lien politique avec la France. Cette thèse analyse la manière dont la souveraineté était comprise et imaginée par les dirigeants français pendant la construction européenne et lors du remodelage de leurs liens avec les anciennes colonies. Sans nier la portée de la souveraineté dans le cadre de l'existence d'un État, elle fut appelée à être modifiée ; ses éléments constitutifs furent repensés au profit d'une forme étatique supranationale. L'étude de ce nouveau modèle des relations internationales sera étendue aux alternatives que les dirigeants français ont proposées aux colonies africaines. Ces derniers les poussaient à dépasser le stade du nationalisme pour adhérer à un modèle étatique jugé supérieur : un stade post-westphalien dans lequel leurs revendications indépendantistes seraient caduques. ; Ravaged by years of occupation, France witnessed major changes in policymakers' vision of the country's future and of French interests and aims. They were aware of the importance of the empire during the war and the role it would play after the war in the restoration of France's international legitimacy as a Great Power. Colonies were also conceived as an essential element of France's revival and of its long-term prosperity. French decision-makers thus sought to strengthen links between the French metropole and its colonies in order to reassess its imperial identity, which was founded on republican principles. These politicians stiffened France's hold on its overseas territories with the implementation of the Union française and gave a second wind to the achievement of a State-Empire. The nineteenth century expansionary phase of the French empire had given way to another phase of imperialism in which development and progress of the overseas territories were at its core. The continuation of the colonial myth had profoundly modified French identity as a key player of the international system. France was no longer seen by its sub-national agents as a simple State holding colonies, but as a new form of statehood; an entity in which its overseas territories was now a constituent part of it and contributed to forging new perspective for their shared future. This new identity had a significant influence on how interests within the international system and particularly in Europe were pursued, especially within the European integration projects. Decisions makers in the French Fourth Republic evaluated their potential gains and preferences, first of all, through the lens of an Imperial Power. In other words, France's political and economic elite had first examined the inherent implications of the upholding of their pre-1940 empire on France's economic and geo-strategic needs, in the shifting context of early Cold War. Pro-European projects were therefore analyzed and weighed in regard to their costs and benefits, in the light of a new grid. Decision makers were influenced by the bien-fondé of French colonialism, based on the sentiment that France had a duty towards overseas territories; a duty of guiding them towards progress and civilization. It is with those considerations in mind that the French governments envisaged another solution to the question of its relationship with its colonies than total independence. The French stance on the European federal project was thus influenced by the introduction of a new variable in the equation of early European integration: the facteur colonial. In the early European integration process, it was considered marginal because of the sectoral approach of the ECSC. Although, the imperial identity was more and more apparent in the interests and policies pursued by the French government during the EDC debate. The introduction of a European army did not ensure France either the possibility of pursuing its peacekeeping operations in the overseas territories or the Indochina War. After the defeat of the EDC project in the French parliament, the government under the leadership of Edgar Faure envisioned a new set of reforms (political, administrative, and economic), which would transform the Union française into a consensual Franco-African federal political association. From this perspective, the ensemble français could not anymore be introduced partially within the European projects promoted in the wake of the « European revival ». Under Guy Mollet's government, a plan to establish supranational structures in their former colonies and in Europe was formulated so that free trade between the two continents could be established. With the economic benefits anticipated for the overseas territories, this Eurafrican project would have proved to African representatives that their interests lay in maintaining the political link between their territories and France. Accordingly, this thesis argues that French leaders questioned the international relations framework based on the nation-state as the central entity of the international system in order to conciliate their ambitions in Europe and as a State-Empire. These two projects – Franco- African association and European integration ̶ shared common characteristics and conceptual origins: supranationalism. French officials and policy-makers promoted a federal Eurafrican project to avoid the process of decolonization and create a political structure that would defuse difficult and pressing colonial issues. The former French colonies were asked to pass from the status of colonized territories to constituents of a supranational structure. The French decision makers pushed the overseas territories to transcend the stage of nationalism to reach an advanced statehood model: a post-Westphalian stage in which their demands for total independence would be obsolete. ; Résumé en espagnol

PMCID: PMC3319317.-- et al. ; [Background]: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). [Methods]: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. [Results]: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10(-3)). [Conclusions]: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. [Impact]: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. ; This research was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This work was also supported by Cancer Research UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). Support was also provided by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. ; A.C. Antoniou is a CR-UK Senior Cancer Research Fellow. D.F. Easton is CR-UK Principal Research Fellow. G. Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was partially supported by Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, the Spanish Ministry of Science and Innovation (FIS PI08 1120), and the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro" to L. Varesco and P. Radice, and "Progetto Tumori Femminili" to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors" to P. Radice), Associazione Italiana per la Ricerca sul Cancro (4017 to P. Pujol), and by funds from Italian citizens who allocated the 5 × 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 × 1000"). ; The DKFZ study was supported by funds from the DKFZ. EMBRACE was supported by CR-UK Grants C1287/A10118 and C1287/A11990. D.G. Evans and Fiona Lalloo were supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R.A. Eeles, Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC). The GEMO study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association "Le cancer du sein, parlons-en!" Award. The Georgetown study was supported by the Familial Cancer Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program—COPTRG) NCI programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical Research Fellow. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the Hungarian Research Grant KTIA-OTKA CK-80745. ICO was supported by Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was supported by a Polish Foundation of Science award to K. Jaworska, a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. ILUH was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. ; INHERIT was supported with J. Simard, Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was supported by Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR), and "Ministero della Salute" ("Progetto Tumori Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9"). kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC [145684, 288704, 454508]. A.-B. Skytte is supported by a NHMRC Senior Research Fellowship. A.K. Godwin was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A.K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. The McGill study was supported by the Jewish General Hospital Weekend to End Breast Cancer. M. Thomassen holds a Fonds de la Recherche en Santé du Québec clinician-scientist award. The MSKCC study was supported by the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative. The NCI study was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. NNPIO was supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency for Science and Innovations (contract 16.512.11.2237). ; OCGN was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. OSU-CCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano Tumori grant to M.A. Caligo. SEABASS was supported by CARIF and University Malaya. The UCSF study was supported by the Helen Diller Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a project grant from CRUK to P.P.D. Pharoah. The UPENN study was supported Komen Foundation for the Cure to S.M. Domchek, the Breast Cancer Research Foundation to K.L. Nathanson, and NIH grants R01-CA083855 and R01-CA102776 to T.R. Rebbeck. WCRI was supported by the American Cancer Society Clinical Research Professorship #SIOP-06-258-06-COUN. ; Peer Reviewed

Las prácticas de defensa y protección de ecosistemas ejercidas por la sociedad civil organizada, representan una valiosa aportación a la comunidad, especialmente si éstas son reconocidas, legitimadas y apoyadas por el Estado. Dichas prácticas constituyen además un semillero para la educación ambiental no formal, promotora de participación social y de ejercicio de ciudadanía en un proceso holístico y retroactivo de enseñanza-aprendizaje, de aprehensión de cambios de conciencia, valores, actitudes, comportamientos, hábitos, conductas, consumos ambientalmente responsables.La educación ambiental no formal puede realizarse desde fuera, a través de un interventor social o un equipo de interventores que llegan a una comunidad, realizan un diagnóstico, definen, aplican y evalúan un programa apropiado para dicha comunidad, buscando siempre que la población se involucre en cada etapa del programa para que se lo apropie y se sienta comprometida con el mismo. Sin embargo, existe mayor riqueza cuando grupos comunitarios y organismos de base, comprometidos y orientados hacia la defensa y protección de ecosistemas terrestres y marinos, son reconocidos y legitimados por el Estado; sus prácticas entonces pueden contribuir a la co-construcción y a la coproducción de políticas públicas ambientales. Es decir, la propia comunidad ejerce ciudadanía y participa con la administración pública en la co-construcción de educación ambiental, de desarrollo local sustentable, de ordenamiento territorial, de definición e implementación de políticas públicas para, posteriormente, poner en práctica lo que se ha construido y llegar así a la co-producción. El siguiente ejemplo puede ilustrar mejor lo anterior……Es el año 1973, la escena se desarrolla en una región rica en recursos naturales, grandes espacios de bosques regados por abundantes manantiales, arroyos, lagos, ríos que cubren el territorio; riqueza y diversidad de flora y fauna están presentes, pero también egoístas ambiciones centradas en el propio beneficio y en el lucro económico. Es evidente que semejante escenario es un atractivo inevitable para industriales y desarrolladores económicos que autoregulan sus actividades justificando la creación de empleos a precio de deforestación y contaminación de suelos, aguas y atmósfera. Hasta aquí, este mismo escenario puede encontrarse actualmente en muy diversas regiones del mundo; este ejemplo hace referencia específicamente a la provincia de Quebec, en Canadá. En este contexto norteamericano, grupos de vecinos se organizaron en esa época para defender su territorio, crearon una red para fortalecerse al agrupar a otros organismos comunitarios. La fuerza de una red era necesaria y continúa siéndolo dado que los intereses del sector privado son frecuentemente apoyados y promovidos por el sector público, quien a su vez tiene también sus propios intereses, no siempre favorables para la población y el medio ambiente. Es así como el ejercicio de la ciudadanía cobró fuerza y grupos similares de la sociedad civil comenzaron a multiplicarse en este territorio, extendiéndose así esta red ambientalista en casi todas las regiones en las que está dividida la provincia de Quebec (en dieciséis de las diecisiete que hay en total).Dicha red es ahora el Consejo Regional del Medio Ambiente (CRE por sus siglas en francés: Conseil regional de l'environnement), organismo sin fines de lucro que en 1995 fue reconocido, legitimado y apoyado por el gobierno de Quebec con una subvención anual; es decir, esta legitimación llegó más de veinte años después de que se creó el primero de estos organismos en la región de Saguenay-Lac-Saint-Jean.Los CRE nacieron del deseo de grupos ambientalistas por crear un organismo regional de concertación en medio ambiente. Se trata de una plataforma que reúne ahora a representantes de otros organismos ambientalistas y sociales de cada región, así como también del sector público, privado, sindicatos, universidades y miembros individuales. Todos ellos voluntariamente se adhieren a esta red de la sociedad civil, con el fin de promover desde la base un desarrollo local sustentable en cada región, incluyendo en esto la difusión de la educación ambiental con programas a escolares, a jóvenes y a adultos, a ribereños para el cuidado y protección de sus lagos, a agricultores y ganaderos para el ejercicio sustentable de sus prácticas, etc.Los CRE son organismos de base autónomos; sin embargo, son reconocidos como interlocutores privilegiados del gobierno de Quebec en cuestiones ambientales. Los CRE agrupan a miembros diversos que persiguen objetivos comunes en un ejemplo de gobernanza cívica ambiental. Se trata de una red que representa un actor influyente en el dominio del medio ambiente en Quebec. Considerando las realidades locales y regionales, los CRE privilegian la acción, la concertación, la educación, la información, la sensibilización y el cuidado del medio ambiente para alcanzar sus objetivos. Se suscriben a valores fundamentales como la solidaridad, la equidad, la integridad, el respeto y la democracia (http://rncreq.org/cre.php)Para congregar a los dieciséis CRE, existe el RNCREQ (Regroupement national des conseils régionaux de l'environnement du Québec, http://rncreq.org/), organismo sin fines de lucro que además busca defender el derecho de los ciudadanos a participar en debates públicos, principalmente los organizados por el BAPE (Bureau d'audiences publiques sur l'environnement), instancia pública del gobierno provincial. El BAPE da a conocer en audiencias públicas los proyectos de desarrollo local o que competen al medio ambiente, esto con el fin de que la sociedad civil y los diversos actores sociales manifiesten su aceptación o rechazo del proyecto propuesto generalmente por los sectores público y privado (http://www.bape.gouv.qc.ca/).El RNCREQ, a través de los 16 CRE que se encuentran en la provincia de Quebec, agrupa actualmente a 1,850 miembros, divididos de la siguiente forma: 351 pertenecientes a organismos ambientalistas; 363 a gobiernos locales; 274 a organismos públicos; 149 a corporaciones privadas; 543 son miembros individuales y 170 tienen otras adscripciones.Este ejemplo permite apreciar la fuerza adquirida por la sociedad civil organizada cuando es ella misma quien se apropia de su territorio, defiende y protege sus ecosistemas mediante prácticas legitimadas y apoyadas por un Estado democrático, creador de espacios para promoción y desarrollo de ejercicio de ciudadanía.Por otro lado, el estado de Veracruz, en México, rico en recursos naturales, está dividido en diez regiones dentro de las cuales hay diversos grupos comunitarios y ONG comprometidos con la defensa y protección del medio ambiente; la población que participa en este tipo de organismos ya cuenta con un cierto nivel de educación ambiental y practica el ejercicio de su ciudadanía, además son ellos quienes mejor conocen su entorno. Sin embargo, entre otras cosas, falta aún la fuerza que puede proporcionar un organismo red, legitimado y autónomo, como plataforma para congregar a representantes de otros organismos comunitarios, grupos de vecinos, individuos y miembros del sector público y privado interesados en participar en la defensa y protección de los ecosistemas de cada región.Recientemente, la Comisión de Medio Ambiente, Recursos Naturales y Aguas del Congreso de Veracruz, presentó una iniciativa de reforma al artículo 186 de la Ley Estatal de Protección Ambiental; dicha reforma ya fue aprobada y tiene la finalidad de crear en cada Ayuntamiento del estado de Veracruz el Consejo Municipal de Medio Ambiente y Desarrollo Sustentable. Se busca que dicho Consejo permita la participación de ciudadanos, académicos, empresarios y funcionarios municipales en la proposición de estrategias, acciones, políticas públicas, toma de decisiones en temas ambientales y vigilancia del manejo del presupuesto destinado a la protección del medio ambiente, gozando además de autonomía aunque se trate de organismos públicos. Habrá entonces 212 Consejos de este tipo en todo el estado, uno en cada municipio, en los próximos tres meses, plazo que se fijó para su instalación.[1] Quizá sería entonces conveniente que en cada una de las diez regiones del territorio veracruzano se instalara también un Consejo Regional responsable de dar seguimiento a las actividades, programas y propuestas realizadas por cada uno de los Consejos Municipales de su territorio; esto, porque supervisar a 212 Consejos parece más complejo. Además, la cercanía entre los municipios hace que algunos de los problemas que afectan al medio ambiente y a la población sean comunes entre ellos; se pueden permitir entonces alianzas intermunicipales, trabajo en proyectos conjuntos, optimización de recursos y fuerza con la participación de más actores sociales.A diferencia del ejemplo de los CRE en la provincia de Quebec, los Consejos Municipales de Medio Ambiente y Desarrollo Sustentable que se instalarán en el estado de Veracruz no son precisamente una iniciativa de la sociedad civil. Se trata sin embargo de una buena iniciativa del Estado; sólo se espera que realmente se escuchen y se favorezcan los intereses de la población y que la orientación sea hacia un verdadero desarrollo local sustentable, en un contexto de equidad, de democracia, de autonomía, de justicia social y ambiental. [1]http://hoyveracruz.com.mx/notas/14719/Corre-plazo-para-crear-consejos-municipales-de-medio-Ambiente.html. http://www.veracruzanos.info/2011/05/presenta-ainara-rementeria-iniciativa-de-reforma-a-ley-estatal-de-proteccion-ambiental/

Publisher's version (útgefin grein) ; Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors. ; Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the "Fondo Europeo de Desarrollo Regional, una manera de hacer Europa" (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. BCAC: we thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Tu Nguyen-Dumont is a National Breast Cancer Foundation (Australia) Career Development Fellow. ABCS thanks the Blood bank Sanquin, The Netherlands. Samples are made available to researchers on a non-exclusive basis. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. Hedy Rennert, Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Muñoz Garzón, Alejandro Novo Domínguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Peña Fernández, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), José Antúnez, Máximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigación Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquín González-Carreró and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. Investigators from the CPS-II cohort thank the participants and Study Management Group for their invaluable contributions to this research. They also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. FHRISK thanks NIHR for funding. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Kröber and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nüchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Heidi Toiminen, Kristiina Aittomäki, Irja Erkkilä and Outi Malkavaara. HMBCS thanks Peter Hillemanns, Hans Christiansen and Johann H. Karstens. HUBCS thanks Shamil Gantsev. KARMA thanks the Swedish Medical Research Counsel. KBCP thanks Eija Myöhänen, Helena Kemiläinen. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MABCS thanks Milena Jakimovska (RCGEB "Georgi D. Efremov), Katerina Kubelka, Mitko Karadjozov (Adzibadem-Sistina" Hospital), Andrej Arsovski and Liljana Stojanovska (Re-Medika" Hospital) for their contributions and commitment to this study. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group) thanks Daniela Zaffaroni, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines and Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Québec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skillful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. NBHS thanks study participants and research staff for their contributions and commitment to the studies. We would like to thank the participants and staff of the Nurses' Health Study and Nurses' Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander and Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao and Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. PREFACE thanks Sonja Oeser and Silke Landrith. PROCAS thanks NIHR for funding. RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Anja Kromwijk-Nieuwlaat, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. We thank the SUCCESS Study teams in Munich, Duessldorf, Erlangen and Ulm. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. CIMBA: we are grateful to all the families and clinicians who contribute to the studies; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Griškevičius; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), thanks in particular: Giulia Cagnoli, Roberta Villa, Irene Feroce, Mariarosaria Calvello, Riccardo Dolcetti, Giuseppe Giannini, Laura Papi, Gabriele Lorenzo Capone, Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato, Isabella Marchi, Elena Bandieri, Antonio Russo, Daniele Calistri and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. FPGMX: members of the Cancer Genetics group (IDIS): Ana Blanco, Miguel Aguado, Uxía Esperón and Belinda Rodríguez. We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Diana Torres, Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Mélanie Léoné, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valérie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study. Drs.Sofia Khan, Irja Erkkilä and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C.M. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): A.W. van den Belt-Dusebout. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Overbeek; the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Aniko Bozsik, Zoltan Matrai, Miklos Kasler, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clinicians and patients for their contributions to this study; HVH (University Hospital Vall d'Hebron) the authors acknowledge the Oncogenetics Group (VHIO) and the High Risk and Cancer Prevention Unit of the University Hospital Vall d'Hebron, Miguel Servet Progam (CP10/00617), and the Cellex Foundation for providing research facilities and equipment; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab investigators, research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O'Conor; Christina Selkirk; Helena Jernström, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna Öfverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellström Pigg, Richard Rosenquist; from Linköping University Hospital: Marie Stenmark-Askmalm, Sigrun Liedgren; Cecilia Zvocec, Qun Niu; Joyce Seldon and Lorna Kwan; Dr. Robert Nussbaum, Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad and Salina Chan; Carole Pye, Patricia Harrington and Eva Wozniak. OSUCCG thanks Kevin Sweet, Caroline Craven, Julia Cooper, Michelle O'Conor and Amber Aeilts. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l'Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BCINIS study was funded by the BCRF (The Breast Cancer Research Foundation, USA). The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, K05 CA136967, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the German Research Foundation (Do 761/10-1). The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. E.K was supported by the program for support the bioresource collections №007-030164/2 and study was performed as part of the assignment of the Ministry of Science and Higher Education of Russian Federation (№АААА-А16-116020350032-1). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. LMBC is supported by the 'Stichting tegen Kanker'. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov" and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 × 1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council [grant 2017-00644 for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER)]. The SZBCS is financially supported under the program of Minister of Science and Higher Education "Regional Initiative of Excellence" in years 2019-2022, Grant No 002/RID/2018/19. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. CIMBA CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015 and Nr. P-MIP-19-164. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Funds from Italian citizens who allocated the 5 × 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5 × 1000') to S. Manoukian. UNIROMA1: Italian Association for Cancer Research (AIRC; grant no. 21389) to L. Ottini. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: NIH/NCI grant P30-CA006927. The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. Ana Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the French National Institute of Cancer (INCa) (grants AOR 01 082, 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015) and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). GEORGETOWN: the Survey, Recruitment and Biospecimen Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008) and the Fisher Center for Hereditary Cancer and Clinical Genomics Research. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and NKFI_OTKA K-112228. HVH (University Hospital Vall d'Hebron) This work was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds: FIS PI12/02585 and PI15/00355. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and "Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa" (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, P18/01029, and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338, 2017SGR449, and PERIS Project MedPerCan), and CERCA program. IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and "5 × 1000" Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-45012). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: was funded by the Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Researc h UK. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. ; Peer Reviewed

This Report documents the presentations given at the World's first international conference on the management value of the resource knowledge of small scale, indigenous and commercial fishers. The conference was inspired by Dr Robert (Bob) Johannes, whose 1981 Book 'Words of the Lagoon', was the first serious study in this area, and was co-hosted by the UBC Fisheries Centre, UBC First Nations House of Learning and the BC Aboriginal Fisheries Commission. Over 200 people representing 23 countries and 36 North American First Nation representatives attended. The conference sought to provide a way to 'step beyond' fishers' frustration that their knowledge is ignored and scientists' standard position that the knowledge is anecdotal, and can not easily be captured in the reports, tables and graphs they are used to. In total, 48 papers and 26 abstracts of papers were presented during the three days of the conference. These case studies and presentations included Indigenous, Artisanal, small scale and industrial marine and freshwater fisheries in tropical and temperate environments. Species range from turtles and dugongs, through temperate trawl and tropical multi-species fisheries to the aquarium trade. The conference followed themes relating to the use of fishers' ecological knowledge about fishing practices in environmental management; the relationships between fishers' expertise (knowledge) and management; methodological issues/methods for obtaining and accurately representing fishers' knowledge; the ethical issues relating to collaboration between TEK practitioners, managers, academics and industry; and the valuation of fishers' knowledge from an ecological, economic and social approach. DIRECTOR'S FOREWORD -- CONTRIBUTED PAPERS -- MY GRANDFATHER'S KNOWLEDGE: FIRST NATIONS FISHING METHODOLOGIES IN THE MID FRASER RIVER (Arnie Narcisse) -- A NATIVE CHANT Simon Lucas -- FISHERS' KNOWLEDGE AND MANAGEMENT: DIFFERING FUNDAMENTALS IN ARTISANAL AND INDUSTRIAL FISHERIES (R.E. Johannes) -- THE ROLE OF FISHERS KNOWLEDGE IN IMPLEMENTING OCEAN ACT INITIATIVES IN NEWFOUNDLAND AND LABRADOR (A. S. Power and Dawn) Mercer) -- CLOSING THE LOOP: COMMERCIAL FISH HARVESTERS' LOCAL ECOLOGICAL KNOWLEDGE AND SCIENCE IN A STUDY OF COASTAL COD IN NEWFOUNDLAND AND LABRADOR, CANADA (Karen Gosse, Joe Wroblewski and Barbara Neis) -- APPLYING LOCAL AND SCIENTIFIC KNOWLEDGE TO THE ESTABLISHMENT OF A SUSTAINABLE FISHERY: THE CURRENT WEST COAST VANCOUVER ISLAND GOOSE BARNACLE FISHERY EXPERIENCE (Joanne Lessard , Josie Osborne, Ray Lauzier, Glen Jamieson and Rick Harbo) -- PARTICIPATORY RESEARCH IN THE BRITISH COLUMBIA GROUNDFISH FISHERY. (Richard D. Stanley and J. Rice) -- THE DISCOURSE OF PARTICIPATORY DEMOCRACY IN MARINE FISHERIES MANAGEMENT (Heidi Glaesel and Mark Simonitsch) -- THE ROLE OF INDIGENOUS KNOWLEDGE IN DEPLETING A LIMITED RESOURCE – A CASE STUDY OF THE BUMPHEAD PARROTFISH (BOLBOMETOPON MURICATUM) ARTISANAL FISHERY IN ROVIANA LAGOON, WESTERN PROVINCE, SOLOMON ISLANDS (Richard Hamilton) -- USING FISHERS' KNOWLEDGE GOES BEYOND FILLING GAPS IN SCIENTIFIC KNOWLEDGE – ANALYSIS OF AUSTRALIAN EXPERIENCES (Pascale Baelde) -- LOCAL ECOLOGICAL KNOWLEDGE AND SMALL-SCALE FISHERIES MANAGEMENT IN THE MEKONG RIVER IN SOUTHERN LAOS(Ian Baird) -- SCIAENID AGGREGATIONS IN NORTHERN AUSTRALIA: AN EXAMPLE OF SUCCESSFUL OUTCOMES THROUGH COLLABORATIVE RESEARCH. (M.J. Phelan) -- STATUS OF RESEARCH ON INDIGENOUS FISHERS' KNOWLEDGE IN AUSTRALIA AND BRAZIL (Adam Faulkner and Renato A. M. Silvano) -- TRADITIONAL MARINE RESOURCE MANAGEMENT IN VANUATU – SACRED & PROFANE: WORLD VIEWS IN TRANSFORMATION (Francis Hickey) ACCOUNTING FOR THE IMPACTS OF FISHERS' KNOWLEDGE AND NORMS ON ECONOMIC EFFICIENCY (Murray A. Rudd) -- THE USE OF FISHERS' KNOWLEDGE IN THE MANAGEMENT OF FISH RESOURCES IN MALAWI(Edward Nsiku) -- EXAMINING THE TWO CULTURES THEORY OF FISHERIES KNOWLEDGE: THE CASE OF THE NORTHWEST ATLANTIC BLUEFISH (Douglas Wilson) THE VALUE OF LOCAL KNOWLEDGE IN SEA TURTLE CONSERVATION: A CASE FROM BAJA CALIFORNIA, MEXICO (Kristin E. Bird, Wallace J. Nichols and Charles R. Tambiah) -- PUTTING FISHERMEN'S KNOWLEDGE TO WORK: THE PROMISE AND PITFALLS (Ted Ames) -- USING EXPERT KNOWLEDGE TO IDENTIFY POSSIBLE GROUNDFISH 'ESSENTIAL FISH HABITATS' (Melanie Bergmann, B. Hinz, R. Blyth, M.J. Kaiser, S.I. Rogers and M. Armstrong) -- INTEGRATION OF FISHERS' KNOWLEDGE INTO RESEARCH ON A LARGE TROPICAL RIVER BASIN, THE MEKONG RIVER IN SOUTHEAST ASIA (Anders F. Poulsen) -- FISHERS' PERCEPTIONS ON THE SEAHORSE FISHERY IN CENTRAL PHILIPPINES: INTERACTIVE APPROACHES AND AN EVALUATION OF RESULTS (J. Meeuwig, M.A. Samoilys and J. Erediano) -- FOCUSING AND TESTING FISHER KNOW-HOW TO SOLVE CONSERVATION PROBLEMS (Edward F. Melvin and Julia K Parrish) -- BIOLOGY AND MANAGEMENT USING KNOWLEDGE REPRESENTATION [ARTIFICIAL INTELLIGENCE] (Antonio García-Allut, Juan Freire, Alvaro Barreiro and David E. Losada) -- INTEGRATING FISHERS' KNOWLEDGE WITH SURVEY DATA TO UNDERSTAND THE STRUCTURE, ECOLOGY AND USE OF A SEASCAPE OFF SOUTHEASTERN AUSTRALIA (Alan Williams and Nic Bax) -- 'SUSTAINABILITY VECTORS' AS GUIDES IN FISHERIES MANAGEMENT: WITH EXAMPLES FROM NET FISHERIES IN THE PHILIPPINES AND AUSTRALIA (Michael D Pido, Peter Valentine and Mark Fenton) -- FISHERS AND SCIENTISTS: NO LONGER FOE, BUT NOT YET FRIEND (Melanie D. Power and Ratana Chuenpagdee) -- HARVESTING AN INLAND SEA: FOLK HISTORY, TEK AND THE CLAIMS OF LAKE MICHIGAN'S COMMERCIAL FISHERY (Michael Chiarappa) -- CAN HISTORICAL NAMES & FISHERS' KNOWLEDGE HELP TO RECONSTRUCT LAKES? (Johan Spens) -- EXPLORING CULTURAL CONSTRUCTS: THE CASE OF SEA MULLET MANAGEMENT IN MORETON BAY, SOUTH EAST QUEENSLAND, AUSTRALIA (Tanuja Barker and Annie Ross) -- WHO'S LISTENING? ISLANDER KNOWLEDGE IN FISHERIES MANAGEMENT IN TORRES STRAIT, NORTHERN AUSTRALIA (Monica E. Mulrennan) -- A COLLABORATIVE, CONSULTATIVE AND COMMITTED APPROACH TO EFFECTIVE MANAGEMENT OF DUGONGS IN TORRES STRAIT, QUEENSLAND, AUSTRALIA. (Donna Kwan) -- FISHING FOR ANSWERS: THE INCORPORATION OF INDIGENOUS KNOWLEDGE IN NORTHERN AUSTRALIA: DEVELOPING CROSS CULTURAL LITERACY (Melissa Nursey-Bray) THE USE OF TRADITIONAL HAWAIIAN KNOWLEDGE IN THE CONTEMPORARY MANAGEMENT OF MARINE RESOURCES(Kelson "Mac" Poepoe, Paul K. Bartram and Alan M. Friedlander) -- TWO FISHERS' KNOWLEDGE SYSTEMS AND FRONTIER STRATEGIES IN THE PHILIPPINES (Maria F. Mangahas) -- HOW SASI PRACTICES MAKE FISHERS' KNOWLEDGE EFFECTIVE (Agus Heri Purnomo) -- HOW LOCAL FISHERS' KNOWLEDGE IMPROVES THE MANAGEMENT OF FISHERIES IN NEW ZEALAND – A SEAFOOD INDUSTRY PERSPECTIVE (G.J. Lydon and A. Langley) -- HISTORICAL AND CURRENT KNOWLEDGE OF THE GREENLAND HALIBUT FROM QUÉBEC FIXED-GEAR FISHERS IN THE GULF OF ST. LAWRENCE (Réjeanne Camirand, Bernard Morin and Louise Savard) -- MARINE RESOURCE KNOWLEDGE RELATED TO FISH CLASSIFICATION IN HAÏTI (Jean W. Wiener) PLATEAU FISHING TECHNOLOGY AND ACTIVITY: STL'ATL'IMX, SECWEPEMC AND NLAKA'PAMUX KNOWLEDGE (Nicholette Prince) -- KAT (AMERICAN EEL, ANGUILLA ROSTRATA) LIFE HISTORY (Kerry Prosper and Mary Jane Paulette) -- THE BARE-FOOT ECOLOGIST'S TOOLBOX (Jeremy D. Prince) -- AN EXAMPLE OF CONSERVATION AND EXPLOITATION ACHIEVED THROUGH A VOLUNTARY FISHERY MANAGEMENT SYSTEM (Robert E. Blyth, Michel J. Kaiser , Paul J.B. Hart and Gareth Edwards-Jones) -- INTEGRATING SCIENTIFIC AND LOCAL ECOLOGICAL KNOWLEDGE (LEK) IN STUDIES OF COMMON EIDERS IN SOUTHERN LABRADOR, CANADA (Heather Chaffey) -- HOW FISHERS' ENDEAVORS AND INFORMATION HELP IN MANAGING THE FISHERIES RESOURCES OF THE SUNDARBAN MANGROVE FOREST OF BANGLADESH (Md. Emdadul Haque) -- WHAT'S IN THERE: COMMON NAMES OF BRAZILIAN MARINE FISHES (Kátia M. F. Freire and Daniel Pauly) -- THE ROLE OF FISHERS' KNOWLEDGE IN CO-MANAGEMENT OF ARTISANAL FISHERIES IN THE ESTUARY OF PATOS LAGOON, SOUTHERN BRAZIL (Daniela Kalikoski, Marcelo Vasconcellos) -- COGNITIVE MAPS: CARTOGRAPHY AND CONCEPTS FOR BACK TO THE FUTURE FISHERIES POLICY (Tony J. Pitcher and Nigel Haggan) -- PAPERS IN ABSTRACT: ORALLY PRESENTED CHANGES IN TECHNOLOGIES, MARKET CONDITIONS, AND SOCIAL RELATIONS: THEIR LINKAGES WITH FISHERS TRADITIONAL ECOLOGICAL KNOWLEDGE (NEW BRUNSWICK'S INSHORE FISHING FLEET IN THE SOUTHERN GULF OF ST.LAWRENCE). (Omer Chouinard and Jean-Paul Vanderlinden) -- FISHING AT KOMODAH, KITKATLA TERRITORY: RETURNING TO SELECTIVITY (Charles R. Menzies and Caroline F.) -- (Butler) -- THE LEADERSHIP ROLE OF CALIFORNIA FISHING MEN AND WOMEN: PROMOTING SCIENCE IN FISHERIES POLICY AND FISH RECOVERY (Natasha Benjamin, Paul Siri and Zeke Grader) -- INCORPORATING INDIGENOUS INTERESTS AND KNOWLEDGE INTO MANAGEMENT OF THE GREAT BARRIER REEF MARINE PARK (M.L. Sommer and L. O. Rosendale) -- USING FISHERS TRADITIONAL KNOWLEDGE TO IDENTIFY PRIORITY AREAS FOR CONSERVATION IN THE PACIFIC OCEAN (Lance Morgan) -- THE NOVA SCOTIA LEATHERBACK TURTLE WORKING GROUP: A MODEL FOR SUCCESSFUL COLLABORATION BETWEEN FISHERS AND SCIENTISTS (Michael C. James and Kathleen E. Martin…) -- TRADITIONAL ECOLOGICAL KNOWLEDGE IN OCEAN AND COASTAL MANAGEMENT: A SURVEY OF RECENT EXPERIENCE IN ATLANTIC CANADA (Paul Macnab and Denise McCullough) -- THE TULALIP TRIBE'S CULTURAL STORIES PROJECT: RECORDING AND USING TRADITIONAL KNOWLEDGE FOR CULTURAL LANDSCAPE RECOVERY, WATERSHED MANAGEMENT AND SALMON PROTECTION (Terry Williams, Julia Gold and Preston Hardison) -- Putting Fishers' Knowledge to Work: Conference Proceedings -- ENVIRONMENTAL SENTINELS: REFRAMING COMMERCIAL FISHING IN PURSUIT OF VALUE, INTEGRITY AND SUSTAINABILITY (Bryan Price) -- DEVELOPING A SET OF INDICATORS FOR EVALUATING THE CONDITION OF A RESOURCE -- CASE: FRESHWATER FISHERIES IN LAOS PDR. (Niels Jepsen, Douglas Wilson & Sommano Phounsavath) -- A METHOD TO ESTIMATE THE ABUNDANCE OF ARAPAIMA GIGAS (CUVIER 1817) -- (Leandro Castello) -- USING FISHERS' KNOWLEDGE TO EVALUATE GREAT LAKES FISHERY MANAGEMENT POLICY (Tracy A. Dobson and Laura F. Cimo) -- THE FISHERMEN AND SCIENTISTS RESEARCH SOCIETY: COLLABORATIVE IMPROVEMENT OF THE KNOWLEDGE BASE FOR MODERN FISHERIES MANAGEMENT (Kees C.T. Zwanenburg1, P. Fanning, P. Hurley and W.T. Stobo) -- FISHERIES IN THE GALÁPAGOS ISLANDS: THE PARTICIPATION OF FISHERS IN FISHERY MANAGEMENT (E. Espinoza, J.C. Murillo, M.V.Toral, R.H. Bustamante, F. Nicolaides, G.J. Edgar, J. Moreno, C. Chasiluisa, M. Yépez, J.C. Barreno, S. A. Shepherd, J. Viscaino, M. Villalta, R. Andrade, A.F. Born, L. Figueroa, P. Guerrero, M. Piu) -- HOW CAN WE HAVE MORE PARTICIPATION BY THE FISHERMEN IN FISHERIES SCIENCE? (Virginia Boudreau) -- THE LEGAL AND INSTITUTIONAL CONTEXT OF INCORPORATING INDIGENOUS KNOWLEDGE INTO FISHERIES MANAGEMENT (Terry Williams and Preston Hardison) -- FISHING IN MURKY WATERS: ETHICS AND POLITICS OF RESEARCH ON FISHER KNOWLEDGE (Anita Maurstad) -- BUILDING NETWORKS FOR INDIGENOUS KNOWLEDGE AND ENVIRONMENTAL MANAGEMENT (Preston Hardison) -- SOCIAL RESEARCH FOR SUSTAINABLE FISHERIES (Christie Dyer and Jessica Paterson) -- ICONS: A SOFTWARE SYSTEM FOR INTEGRATING TRADITIONAL KNOWLEDGE AND NATURAL RESOURCES MANAGEMENT (Preston Hardison and Terry Williams) ASSEMBLY OF MAP-BASED STREAM NARRATIVES TO FACILITATE STAKEHOLDER INVOLVEMENT IN WATERSHED MANAGEMENT (M.R.S. Johannes, K.D. Hyatt, J.K. Cleland, L.Hanslit, and M.M. Stockwell) -- MIGRATION PATTERNS AND SPAWNING HABITS OF AN IMPORTANT FISH, HELIGOPHAGUS WAANDERSI, OF THE PANGASIIDAE FAMILY IN THE MEKONG RIVER BASIN (Sintavong Viravong) -- INSHORE GROUNDFSH SPAWNING AND NURSERY GROUNDS IN THE BAY OF FUNDY: LEARNING WITH AND FROM FISHERMEN (Jennifer Graham) -- THE CONTRIBUTION OF FISHERS TO THE MANAGEMENT OF SEA-URCHIN FISHERIES IN BARBADOS AND ST. LUCIA (Christopher Parker, Patrick McConney and Allan Smith) -- GENERAL DISCUSSION -- LIST OF AUTHORS -- LIST OF PARTICIPANTS ; Fisheries Centre (FC) ; Non UBC ; Unreviewed ; Faculty ; Researcher ; Postdoctoral ; Graduate

Full TextThe Barn Owl The Barn Owl (Tyto alba) is a medium-sized, tawny coloured owl that, with the exception of Antarctica, has worldwide distribution. Like most owls the Barn Owl is considered to be nocturnal. Like all owls, it is predatory bird. In the Barn Owl's case, members of the species are said to enjoy (or specialize, in the biological parlance) in small ground mammals—rodents, for example. In Eastern North America, the majority of their diet would include Meadow Voles (Microtus pennsylvanicus) and Deer Mice (Peromyscus maniculatus). Barn Owls strike a distinct-look with their lack of ear tufts (a misnomer of sorts as the tufts—the "horns" of a Great Horned Owl, Bubo virginianus—are not ears and not associated with hearing at all) and their distinct heart-shaped facial disc (which is associated with hearing, but that's another story for another time). As their common name suggests they can be found living in barns, on a nest made from the regurgitated un-digestible remains of those Meadow Voles and Deer Mice they hunt. Of course Barn Owls are not just limited to barns, but nest in silos, abandoned buildings and tree cavities too. Arguably, this should make their name "Barn, Silo, Abandoned Building & Tree Cavity Owl" but that doesn't really roll off the tongue in the same way. These attributes and distinguishing features are all things to keep in mind if you find yourself out birdwatching near a barn in Southern Ontario. During your explorations, while there are certain to be Rock Pigeons (Columba livia) fluttering about, if you happen to come across a Barn Owl in this setting, you should take notice. Seeing a Barn Owl in Southern Ontario (especially a living Barn Owl) is something to make special note of—it's not a regular occurrence. Part of the significance of seeing a Barn Owl lies in its relative in-abundance. While individuals identified as Tyto alba enjoy a cosmopolitan reputation, Southern Ontario has been considered the northern range of the species ("Ontario Barn Own Recovery Project," 2005) and it has been suggested that Barn Owls have always found, say, other places more to their liking. Because of this, the Barn Owl is a special bird in Canada: it is officially endangered, recognized by the Committee on the Status of Endangered Wildlife in Canada (COSEWIC) ("Ontario Barn Own Recovery Project," 2005). It seems as though Barn Owls living in Ontario have had bad luck of late— of the "handful" ("Ontario Barn Own Recovery Project," 2005 ¶ 4) that have been seen since 1999, two were roadkills ("Ontario Barn Own Recovery Project," 2005) and no breeding pairs have been "confirmed." The Barn Owl of February 27th 2006 If you are a serious birder in Ontario, with a computer and internet access, it is likely that you are aware of the electronic mailing list called Ontbirds. Ontbirds is presented by the self-proclaimed provincial birding association, the Ontario Field Ornithologists. The electronic mailing list (or listserv) is meant to be a clearing-house of bird sightings and directions for interested birders: you read about a bird you would like to see, get the directions and off you go on a (perhaps literal) wild goose chase. On average, four to seven sightings are posted daily. As might be expected, more posting occurs on the weekend, and more postings occur seasonally during spring and fall migration. Typical emails follow a standard form: the subject line contains the bird or birds seen and their location while the body of the email contains more specific information about the birds and precise directions to the location they might be found. While thorough, the information shared is, generally speaking, pretty uncontentious stuff. So, it was with interest that a seemingly normal post on February 28th, 2006 took on new dimensions: whispers of deception, accusation of fraud and, more interestingly for my work, questions of what is normal, known and natural all emerged. On February 28th, 2006, a simple posting appeared in mailboxes of subscribers outlining how a photograph had been taken of a Barn Owl and posted on a webbased photography site. A URL was given linking to the photograph. It was noted that the photographer had not reported seeing the bird on the Ontbirds listserv, but that there was a link to the location where the bird was seen. That same day, the moderator of the listserv posted reminding the subscribers that the Barn Owl was considered "endangered" on breeding territory and that there were rules about posting about endangered birds on the listserv; all of the requirements that needed to be met prior to posting were created in order to reduce the likelihood that an observed bird would abandon a nest or breeding attempt. The following day, March 1st, a conversation had begun via the listserv. Another respondent was interested in knowing more details about the sighting and if the bird had been seen again. The next email later that day was from the photographer himself. In the email, he explained that though he did not remember exactly where he saw the bird, he used Google maps to locate the general location and road names. According to his directions, the Barn Owl was seen in Eastern Ontario, in the Ottawa region. As well, he shared the story of finding the owl, taking the photograph and watching the bird fly away from him. The author also stated that his initial reason for going out birding that day was to find Snowy Owls to photograph and that he had no luck in finding those birds that day. On March 2nd, another email arrived from another Ontbirds subscriber. In it, the author began to question the authenticity of the photograph. This email suggested that the owl's feet have been "doctored," as though something was removed after the photograph had been taken. The author reminded those reading that the Barn Owl is rare for Ontario and especially so where the photograph was taken—the implication being that the bird is so rare that it most likely didn't exist. A third email followed on March 2nd in which the author suggests that there is nothing in the photograph that appears unusual or doctored. The author offered another suggestion about the authenticity of the owl. He reminded us that there was a Barn Owl sighting in a different part of Ontario earlier in the winter and attributes the owl's presence not to digital photographic magic, but to efforts undertaken on the part of humans to help the species recover. Yet, this claim to reality does not seem to be working. Later in the afternoon on March 2nd, a fourth email arrived that supports the initial hypothesis that the photograph has been doctored. The author shared that the bird looks like one he had seen at Parc Omega, a wildlife park in Québec, and provides a URL to a photograph of the Parc Omega Barn Owl. The pull of the network to make the photograph unauthentic, and in turn, the owl, continues to mount. In a fifth email, the author shared the contention that the fencepost the Barn Owl is pictured perching on was specially made for captive birds to land on. The author also suggested that given the lighting of the photograph and kind of weather that was observed on the day that the photograph was supposed to have been taken, the photograph could not be discounted as being genuine. This is where the conversation ends on Ontbirds. At 5:30 pm on March 2nd, the listserv co-ordinator posted a message that states that the current conversation on the photographed Barn Owl is inappropriate. The coordinator reminded readers that Ontbirds is not a discussion list and is for "reporting birds period." The closing line in the email reminds readers that not following the guidelines could result in the restriction or loss of being able to post to the listerv. This does not mean, however, that the conversation ended. In following the network thread to a website that catalogues rare birds from the Ottawa area, the sighting details for the Barn Owl seen on February 27th is prefaced with the words "LIKELY HOAX." The page author outlines a litany of evidence that supports his claim that the image has been manipulated. The webpage author concludes his outline with the statement "let the viewer beware." Enacting birds: reflection on the Barn Owl of February 27th I have spent some time thinking about the birders and the Barn Owl. I have read and reflected on the emails and the allegations. From this, themes have emerged concerning the construction of what is natural as well as insights into the creation of what Donna Haraway (2003) calls "naturecultures." Most importantly, this event, be it framed as authentic bird sighting or elaborate hoax, helps enact and make visible a topology of inter-species ethical relations between those who watch birds and the birds they watch. Networks Ontbirds operates within an established network of relations. People post their sightings to share with other interested birders. The process through which experiences are transcribed from embodied encounters to textual references is seemingly an invisible one. In this case, there were visible deviations from the established network. Within the birding community that posts to Ontbirds, the claim to have "found" a bird is an important one. In posts where the author is reporting a first-sighting and they did not find the bird themselves, the name of the bird finder (skilled, lucky or otherwise, as it is never suggested the kind of effort it took to come across the bird) is included. In this example, the finder did not make a submission to Ontbirds to report a rare bird. Rather, it seems like in this case, the original post came via an on-line gallery created by the finder that had the photograph and birding information on it. While never overtly stated, I believe that the authenticity of the Barn Owl was partially called into question due to the fact that the finder of the bird did not post his sighting to the listserv. Additionally, I find interesting to note that in the finder's one email to the Ontbirds listserv, he did his best to fit into the established network. However, problematic for him, he was not familiar with the area where he took the photograph. Part of the established Ontbirds network is knowing where you observed a bird; the more detailed the description of location and directions, the better. In networks, effort is required to maintain the relationships of the actors. The listserv tends to operate with little of what I would call boundary policing on the part of the co-ordinator. What is particularly interesting about the Barn Owl postings was the need of the Ontbirds co-ordinator to make comments concerning the type and quality of postings over the three day period, all referencing the mail about the Barn Owl. In well-established networks, subtle deviations from the established routine lead to powerful reactions: networks tend to become visible when they are threatened. The questioning of the authenticity seems to be such a reaction. What this suggests for a birding network is the power that lies in the focus on names, dates and details. This hybridity that exists between birders and the electronic mailing list certainly has implications in shaping what is considered normal, known and natural for those who subscribe to the list. Birds are enacted through Ontbirds as realities "out there" to be discovered, recorded and reported. While this is not necessarily that surprising, it does, in turn have an impact on other enactments of birds, especially visible in the multiple objects created. Multiple objects In this case there was an exceeding focus by birders on the rarity of the bird, to the point where I believe that the Barn Owl became a multiple object. Emerging from the field of Science and Technology studies, the idea of multiple objects opens a different way to think about the taken-for-granted: objects are often thought of as rigid and immobile in their existence - a Barn Owl will always be a Barn Owl (for a detailed discussion of multiple objects, see Law, 2004; Mol, 2002). In response to this, a multiple version of the object counters this notion of singularity. In focusing on the fractal nature of "reality" and in attending to difference, I believe that this perspective requires attention be paid to the enactment of objects. Enactment, in this sense, is the claim that "relations, and so realities and representations of realities.are being endlessly or chronically brought into being in a continuing process of production and reproduction, and have no status, standing or reality outside those processes" (Law, 2004, p. 159). Enactment is different than constructivism as it does not "imply convergence to singularity," in opposition to the fixing of objects' identities, "but takes difference and multiplicity to be chronic conditions" (Law, 2004, p. 158). Difference suggests that multiple versions of the same object can exist simultaneouslythis occurs because while objects are enacted in practice, these practices can be different. If the practices are different, then so too must be the objects (Law, 2004). Yet these multiple versions-or multiple objectsare, more often than not, able to cohere together. So, if these coherences shape our reality, then reality: is not in principal fixed or singular, and truth is no longer the only ground for accepting or rejecting a representation. The implication is that there are various possible reasons, including the political, for enacting one kind of reality rather than another, and that these grounds can in some measure be debated. (Law, 2004, p. 162) As such, a focus on the enactment of objects is filled with attention to the many ways that actors, human and otherwise, engage to create a reality: a reality described through investigation, a reality that is not the only one "out there" and a reality that focuses on heterogeneity and difference. In the move to collapse multiple realities into one, a distinctly political move is made, where one reality, one particular enactment of an object gains primacy over the others. In this particular becoming of the Barn Owl, the enactment of rarity overshadowed the other ways the bird was known (see Figure 1). Rather than having to pass judgement on if I think the Barn Owl was properly enacted, I think it is more valuable to examine the ways the bird was enacted. Let me outline the different ways (that I can see): - as a rare bird species (through the Ontbirds coordinator, external web pages and some birders' previous knowledge) - as a biological reality (through the email that suggested the Owl was a result of species rebound and human conservation efforts) - as digital magic (many of the claims to digital alteration of the photograph enacted this Barn Owl) - as an Eastern Ontario Barn Owl (through the initial posting) - as an Québec Barn Owl (through the claims it came from Parc Omega) There have also been subtle and tacit ways that the authenticity has been enacted, framed through the network of discovery, recording and reporting previously described. Through these discourses, the Barn Owl has been enacted as a: - valuable, wild bird - feral bird of ambivalent worth - wildlife park captive and therefore does not count In this multiplicity, the Barn Owl lost value in the eyes of some birders as its authenticity was called into question. What is implicit in this questioning is the understanding that there is some kind of a continuum that reported birds are judged against. It seems that the gold standard of authenticity is one that is wild, rare and (relatively) easy to find. It goes without saying that this perspective is not entirely unproblematic. This, in part, helps explain why there are not any postings to Ontbirds describing a flock of Pigeons seen in a ubiquitous habitat, such as the urbanized core of Anytown, Ontario. A Pigeon simply does not match up to the gold standard of valuable birds. In deciding what gets to "count" in knowledge-making endeavours, and what counts as the gold standard, other birds disappear from what is noticed. In that disappearance, the bird moves to the hinterland. I turn to that next. The hinterland and otherness Hinterland's are an attempt to engage with the act of disappearing. Law puts forward three kinds of Hinterland's: the first, he suggest are "in-here objects" (Law, 2004, p. 55); the second are "visible or relevant out-there contexts" (Law, 2004, p. 55); and the third are "out-there processes, contexts, and all the rest, that are both necessary and necessarily disappear from visibility or relevance" (Law, 2004, p. 55). I would deploy an artistic metaphor of positive space and negative space here: that which is present is the positive space of an image and that which is absent is negative space of an image. It is often difficult to decide if it is the negative or positive space that bounds the image: each side depends on the other such that if one is not there, the known image would disappear. Perhaps, if I expand the metaphor, the hidden absent is that which is not within the frame of the image. Importantly, all that lies outside the frame, while unnecessary in the composition of the image, is only unnecessary because it has been selectively ignored in the composition of the image. Emerging from this perspective on the hinterland is the acknowledgement that a relationship with the unknown, or the other, is necessary; rather than simply ignoring the disappearance, it is an attempt to acknowledge that disappearance is integral to any kind of knowing. Thus, if birding, as an act, continues the "process [of] enacting necessary boundaries between presence, manifest absence and Otherness" (Law, 2004, p. 144), then the various activities taken up in the name of coming to know these organisms are each a distinctly political move, moves that shape and reaffirm (mostly conventional) ways of knowing the nonhuman. For example, the second post in this chain made explicit that the individual Barn Owl was, in fact, part of larger species, Tyto alba and that species was considered to be an endangered one. The term endangered species does just that: focus on species, at the expense of the individual. In this organism's identification as a member of a species, it loses any ability to be something else; what could be has been othered. This act of othering is at times common in birdwatching. It occurs more than once in the Barn Owl discussion: through the questioning about the validity of the sighting, the focus subtly shifts from the sighting to determining the authenticity of the photograph. Again, in this move the individual owl disappears. The Barn Owl was not the only member of the order Aves to be othered in this particular natureculture assemblage. It is also interesting to note that the Snowy Owls, the birds that were the original objective of the outing that produced the Barn Owl, have disappeared. Likely, there were other birds seen during that trip, but for whatever reason (perhaps not rare, not big, not charismatic), they were ignored. For my purposes, I consider this othering problematic, in part, because it does little to acknowledge the lived experiences of nonhuman individuals. The challenge here is that the act of othering, in and of itself, is not inherently wrong. Rather than focusing on what might be out there, I believe that it is important to be able to recognize enactments that are politically aligned with the kind of relationships that ought to exist. So, one needs to develop the skill of attending to what is observably cast to the hinterland and what is brought to the forefront. In a sense, this is what I've attempted to do with my analysis of the Barn Owl narrative and the creation of the enacted set of relations in Figure 1. In creating this particular map of relations, I attempt to move beyond the established frame and re-focus on those multiple enactments that have been cast aside. In so doing, political actions and entrenched positions are more easily visible, while others can re-emerge from obscurity. It is true that there might be other unknowable enactments that exist in the hinterland-but let me suggest that acknowledging that, at best, partial perspectives (Haraway, 1991) are our best version of reality (as a nod to multiplicity does) offers more space for other realities to emerge. Thinking more generally about our dominant cultural relationship with the nonhuman, the promise of attentiveness to the various enactments of animals offer the opportunity to intentionally enact a reality that is more in line with one's own ethics. In asking what practices of birding are good or which practices ought we to be enacting, attention can be turned to current enactments to ask: "Ought they be enacted in this way?" This simple question, paired with the knowledge that there are other enactments hidden, could be enough to continue to question some of our Western culture's taken-forgranted assumptions about what it is to be human and otherwise. References Haraway, D. (1991). Situated knowledges: The science question in feminism and the privilege of partial perspective. In Simians, Cyborgs, and Women: the reinvention of nature (pp. 183-202). Routledge: New York. Haraway, D. (2003). The companion species manifesto: dogs, people, and significant otherness. Chicago: Prickly Paradigm Press. Law, J. (2004). After method: mess in social science research. London: Routledge. Mol, A. (2002). The body multiple: ontology in medical practice. Durham: Duke University Press. Ontario Barn Own Recovery Project. (2005, February 7). Retrieved March 4, 2006, from http://www.bsc-eoc.org/regional/barnowl.html

Funder: CIMBA: The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A20861, C12292/A11174. ACA is a Cancer Research -UK Senior Cancer Research Fellow. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Québec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research Council of Lithuania grant SEN-18/2015. BIDMC: Breast Cancer Research Foundation. BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT: Associazione Italiana Ricerca sul Cancro (AIRC; IG2014 no.15547) to P. Radice. Italian Association for Cancer Research (AIRC; grant no.16933) to L. Ottini. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. Jacopo Azzollini is supported by funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000'). DEMOKRITOS: European Union (European Social Fund – ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DFKZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by R0 1CA140323, R01 CA214545, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. FPGMX: FISPI05/2275 and Mutua Madrileña Foundation (FMMA). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HRBCP: Hong Kong Sanatorium and Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health1R 03CA130065, and North California Cancer Center. HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: The authors would like to particularly acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and "Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa" (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). IHCC: PBZ_KBN_122/P05/2004. ILUH: Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and "5x1000" Istituto Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MODSQUAD: MH CZ - DRO (MMCI, 00209805), MEYS - NPS I - LO1413 to LF and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NAROD: 1R01 CA149429-01. NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NICCC: Clalit Health Services in Israel, the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. NNPIO: the Russian Foundation for Basic Research (grants 17-54-12007, 17-00-00171 and 18-515-12007). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) grant 2014-2015-2016. SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032, P20CA233307, American Cancer Society (MRSG-13-063-01-TBG, CRP-10-119-01-CCE), Breast Cancer Research Foundation, Susan G. Komen Foundation (SAC110026), and Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance. Mr. Qian was supported by the Alpha Omega Alpha Carolyn L. Cuckein Student Research Fellowship. UCLA: Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR: Cancer Research UK. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. ; Abstract: Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94–1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85–1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06–1.48) and HR = 1.59 (95% CI: 1.08–2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

Under a Creative Commons license.-- Review.-- et al. ; Targeted therapies and the consequent adoption of >personalized> oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity >broad-spectrum> therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered. ; Amr Amin was funded by Terry Fox Foundation Grant # TF-13-20 and UAEU Program for Advanced Research (UPAR) #31S118; Jack Arbiser was funded by NIHAR47901; Alexandra Arreola was funded by NIH NRSA Grant F31CA154080; Alla Arzumanyan was funded by NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer (AI076535); Work in the lab of Asfar S. Azmi is supported by NIH R21CA188818 as well as from Sky Foundation Inc. Michigan; Fabian Benencia was supported by NIH Grant R15 CA137499-01; Alan Bilsland was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Amancio Carnero was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). His work on this project has also been made possible thanks to the Grant PIE13/0004 co-funded by the ISCIII and FEDER funds; Stephanie C. Casey was supported by NIH Grant F32CA177139; Mrinmay Chakrabarti was supported by the United Soybean Board; Rupesh Chaturvedi was supported by an NIH NCCAM Grant (K01AT007324); Georgia Zhuo Chen was supported by an NIH NCI Grant (R33 CA161873-02); Helen Chen acknowledges financial support from the Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Sophie Chen acknowledges financial support from the Ovarian and Prostate Cancer Research Trust, UK; Yi Charlie Chen acknowledges financial support from the West Virginia Higher Education Policy Commission/Division of Science Research, his research was also supported by NIH grants (P20RR016477 and P20GM103434) from the National Institutes of Health awarded to the West Virginia IDeA Network of Biomedical Research Excellence; Maria Rosa Ciriolo was partially supported by the Italian Association for Cancer Research (AIRC) Grants #IG10636 and #15403; Helen M. Coley acknowledges financial support from the GRACE Charity, UK and the Breast Cancer Campaign, UK; Marisa Connell was supported by a Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Sarah Crawford was supported by a research grant from Connecticut State University; Charlotta Dabrosin acknowledges financial support from the Swedish Research Council and the Swedish Research Society; Giovanna Damia gratefully acknowledges the generous contributions of The Italian Association for Cancer Research (IG14536 to G.D.); ; Santanu Dasgupta gratefully acknowledges the support of the University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; William K. Decker was supported in part by CPRIT, the Cancer Prevention and Research Institute of Texas; Anna Mae E. Diehl was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA), Gilead and Shire Pharmaceuticals; Q. Ping Dou was partially supported by NIH/NCI (1R01CA20009, 5R01CA127258-05 and R21CA184788), and NIH P30 CA22453 (to Karmanos Cancer Institute); Janice E. Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division; Eyad Elkord thanks the National Research Foundation, United Arab Emirates University and the Terry Fox Foundation for supporting research projects in his lab; Bassel El-Rayes was supported by Novartis Pharmaceutical, Aveo Pharmaceutical, Roche, Bristol Myers Squibb, Bayer Pharmaceutical, Pfizer, and Kyowa Kirin; Mark A. Feitelson was supported by NIH/NIAID Grant AI076535; ; Dean W. Felsher was supported by NIH grants (R01CA170378, U54CA149145, and U54CA143907); Lynnette R Ferguson was financially supported by the Auckland Cancer Society and the Cancer Society of New Zealand; Gary L. Firestone was supported by NIH Public Service Grant CA164095 awarded from the National Cancer Institute; Christian Frezza "would like to acknowledge funding from a Medical Research Council CCU-Program Grant on cancer metabolism, and a unique applicant AICR project grant"; Mark M. Fuster was supported by NIH Grant R01-HL107652; Alexandros G. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program 'Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES (Grant number MIS 379346) and COST Action CM1201 'Biomimetic Radical Chemistry'; Michelle F. Green was supported by a Duke University Molecular Cancer Biology T32 Training Grant; Brendan Grue was supported by a National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Dorota Halicka was supported by by NIH NCI grant NCI RO1 28704; Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, by the Czech Science Foundation projects 15-03834Y and P301/12/1686, by the Czech Health Research Council AZV project 15-32432A, and by the Internal Grant Agency of the Ministry of Health of the Czech Republic project NT13663-3/2012; Matthew D. Hirschey wishes to acknowledge Duke University Institutional Support, the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the National Institute of Aging (P30AG028716-01) and NIH/NCI training grants to Duke University (T32-CA059365-19 and 5T32-CA059365); ; Lorne J. Hofseth was supported by NIH grants (1R01CA151304, 1R03CA1711326, and 1P01AT003961); Kanya Honoki was supported in part by the grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24590493); Hsue-Yin Hsu was supported in part by grants from the Ministry of Health and Welfare (CCMP101-RD-031 and CCMP102-RD-112) and Tzu-Chi University (61040055-10) of Taiwan; Lasse D. Jensen was supported by Svenska Sallskapet for Medicinsk Forskning, Gosta Fraenkels Stiftelse, Ak.e Wibergs Stiftelse, Ollie och Elof Ericssons Stiftelse, Linkopings Universitet and the Karolinska Institute, Sweden; Wen G. Jiang wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Lee W. Jones was supported in part by grants from the NIH NCI; W Nicol Keith was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www.cancerresearchuk.org) Grant C301/A14762; Sid P. Kerkar was supported by the NIH Intramural Research Program; Rob J. Kulathinal was supported by the National Science Foundation, and the American Cancer Society; Byoung S. Kwon was supported in part by National Cancer Center (NCC-1310430-2) and National Research Foundation (NRF-2005-0093837); Anne Le was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, a Lustgarten Fund Grant 90049125 and Grant NIHR21CA169757 (to Anne Le); Michael A. Lea was funded by the The Alma Toorock Memorial for Cancer Research; Ho-Young Lee. ; This work was supported by grants from the National Research Foundation of Korea (NRF), the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea (Nos. 2011-0017639 and 2011-0030001) and by a NIH Grant R01 CA100816; Liang-Tzung Lin was supported in part by a grant from the Ministry of Education of Taiwan (TMUTOP103005-4); Jason W. Locasale acknowledges support from NIH awards (CA168997 and AI110613) and the International Life Sciences Institute; Bal L. Lokeshwar was supported in part by United States' Public Health Services Grants: NIH R01CA156776 and VA-BLR&D Merit Review Grant No. 5I01-BX001517-02; Valter D. Longo acknowledges support from NIH awards (P01AG034906 and R01AG020642) and from the V Foundation; Costas A. Lyssiotis was funded in part by the Pancreatic Cancer Action Network as a Pathway to Leadership Fellow and through a Dale F. Frey Breakthrough award from the Damon Runyon Cancer Research Foundation; Karen L. MacKenzie wishes to acknowledge the support from the Children's Cancer Institute Australia (affiliated with the University of New South Wales, Australia and the Sydney Children's Hospital Network); Maria Marino was supported by grant from University Roma Tre to M.M. (CLA 2013) and by the Italian Association for Cancer Research (AIRC-Grant #IG15221); ; Ander Matheu is funded by Carlos III Health Institute (AM: CP10/00539), Basque Foundation for Science (IKERBASQUE) and Marie Curie CIG Grant (AM: 2012/712404); Christopher Maxwell was supported by funding from the Canadian Institutes of Health Research, in partnership with the Avon Foundation for Women (OBC-134038) and the Canadian Institutes of Health Research New Investigator Salary Award (MSH-136647); Eoin McDonnell received Duke University Institutional Support; Kapil Mehta was supported by Bayer Healthcare System G4T (Grants4Targets); Gregory A. Michelotti received support from NIH NIDDK, NIH NIAAA, and Shire Pharmaceuticals; Vinayak Muralidhar was supported by the Harvard-MIT Health Sciences and Technology Research Assistantship Award; Elena Niccolai was supported by the Italian Ministry of University and the University of Italy; Virginia R. Parslow gratefully acknowledges the financial support of the Auckland Cancer Society Research Centre (ACSRC); Graham Pawelec was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) Grant number 16SV5536K, and by the European Commission (FP7 259679 "IDEAL"); Peter L. Pedersen was supported by NIH Grant CA-10951; Brad Poore was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, the Lustgarten Fund Grant 90049125, and Grant NIHR21CA169757 (to Anne Le); Satya Prakash was supported by a Canadian Institutes of Health Research Grant (MOP 64308); Lizzia Raffaghello was supported by an NIH Grant (P01AG034906-01A1) and Cinque per Mille dell'IRPEF–Finanziamento della Ricerca Sanitaria; Jeffrey C. Rathmell was supported by an NIH Grant (R01HL108006); Swapan K. Ray was supported by the United Soybean Board; Domenico Ribatti received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under Grant agreement n°278570; Luigi Ricciardiello was supported by the AIRC Investigator Grants 10216 and 13837, and the European Community's Seventh Framework Program FP7/2007–2013 under Grant agreement 311876; Francis Rodier acknowledges the support of the Canadian Institute for Health Research (FR: MOP114962, MOP125857), Fonds de Recherche Québec Santé (FR: 22624), and the Terry Fox Research Institute (FR: 1030); ; Gian Luigi Russo contributed to this effort while participating in the Fulbright Research Scholar Program 2013–14; Isidro Sanchez-Garcia is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH Grant (R01 CA109335-04A1), by Junta de Castilla y León (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). Isidro Sanchez-Garcia's lab is also a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program; Andrew J. Sanders wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Neeraj K. Saxena was supported by grant funding from NIH NIDDK (K01DK077137, R03DK089130); Dipali Sharma was partially funded by NIH NCI grants (R01CA131294, R21 CA155686), the Avon Foundation and a Breast Cancer Research Foundation Grant (90047965); Markus David Siegelin received funding from National Institute of Health, NINDS Grant K08NS083732, and the 2013 AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research, Grant Number 13-20-23-SIEG; Neetu Singh was supported by funds from the Department of Science and Technology (SR/FT/LS-063/2008), New Delhi, India; Carl Smythe was supported by Yorkshire Cancer Research and The Wellcome Trust, UK; Carmela Spagnuolo was supported by funding from Project C.I.S.I.A., act n. 191/2009 from the Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region 2007/2013, objectives 2.1, 2.2; Diana M. Stafforini was supported by grants from the National Cancer Institute (5P01CA073992), IDEA Award W81XWH-12-1-0515 from the Department of Defense, and by the Huntsman Cancer Foundation; John Stagg was supported by the Canadian Institutes of Health Research; Pochi R. Subbarayan was supported by the University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant (CTSI-2013-P03) and SEEDS You Choose Awards; Phuoc T. Tran was funded by the DoD (W81XWH-11-1-0272 and W81XWH-13-1-0182), a Kimmel Translational Science Award (SKF-13-021), an ACS Scholar award (122688-RSG-12-196-01-TBG) and the NIH (R01CA166348); Kathryn E. Wellen receives funding from the National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts, American Diabetes Association, and Elsa U. Pardee Foundation; Huanjie Yang was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLXS011); ; Paul Yaswen was supported by funding from the United States National Institutes of Health (ES019458) and the California Breast Cancer Research Program (17UB-8708); Clement Yedjou was supported by a grant from the National Institutes of Health (Grant # G1200MD007581), through the RCMI-Center for Environmental Health; Xin Yin was supported by NIH/National Heart, Lung, and Blood Institute Training Grant T32HL098062.; Jiyue Zhu was supported by NIH Grant R01GM071725; Massimo Zollo was supported by the European FP7-TuMIC HEALTH-F2-2008-201662, the Italian Association for Cancer research (AIRC) Grant IG # 11963 and the Regione Campania L.R:N.5, the European National Funds PON01-02388/1 2007-2013. ; Peer Reviewed

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Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis. ; he authors in this manuscript were working on behalf of BCAC, CCFR, CIMBA, CORECT, GECCO, OCAC, PRACTICAL, CRUK, BPC3, CAPS, PEGASUS, TRICL- ILCCO, ABCTB, APCB, BCFR, CONSIT TEAM, EMBRACE, GC-HBOC, GEMO, HEBON, kConFab/AOCS Mod SQuaD, and SWE-BRCA. The breast cancer genome-wide association analyses: BCAC is funded by Cancer Research UK [C1287/A16563, C1287/ A10118], the European Union ' s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST, respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/ A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de lÉconomie, Science et Innovation du Québec through Genome Québec and the PSR-SIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community 's Seventh Framework.Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112 — the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Aus- tralia), and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The ACP study is funded by the Breast Cancer Research Trust, UK. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR-NY, BCFR-PA, and BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy ' s & St. Thomas ' NHS Foundation Trust in partnership with King ' s College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. BOCS is supported by funds from Cancer Research UK (C8620/A8372/A15106) and the Institute of Cancer Research (UK). BOCS acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Co fi nanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + DeI + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Gali- cia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002- C01-7462). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l ' Alimentation, de l ' Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI11/00923 and PI12/00070). COLBCCC is sup- ported by the German Cancer Research Center (DKFZ), Heidelberg, Germany. D.T. was in part supported by a postdoctoral fellowship from the Alexander von Humboldt Foundation. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. H.A.C eceives support from the Lon V Smith Foundation (LVS39420). The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charit.No. 1121258 and the NCRN. The coordination of EPIC is fi nancially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l ' Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Neth- erlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC- Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC- Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Kreb- shilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (Ger- man Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713- 241202, 713-241202, 14505/2470, and 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). GLACIER was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy ' s and St Thomas ' NHS Foundation Trust and King ' s College London. The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf- Bartling Foundation. The HEBCS was fi nancially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan, by National Cancer Center Research and Development Fund, and " Practical Research for Innovative Cancer Control (15ck0106177h0001) " from Japan Agency for Medical Research and develop- ment, AMED, and Cancer Bio Bank Aichi. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scienti fi c Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014, and 17-44-020498. ICICLE was supported by Breast Cancer Now, CRUK, and Biomedical Research Centre at Guy ' s and St Thomas ' NHS Foundation Trust and King ' s College London. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (A.L. F.) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was fi nancially supported by the special Government Funding (E.V. O.) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.-T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. The KOHBRA study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). LAABC is supported by grants (1RB-0287, 3PB- 0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. TheCSP is also part of the National Cancer Institute ' s Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. L.M.B.C. is supported by the ' Stichting tegen Kanker ' . D.L. is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology " Georgi D. Efremov " and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Edu- cation and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects " 5 × 1000 " ). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839, and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foun- dation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286, and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the " CIHR Team in Familial Risks of Breast Cancer " program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/ 06) and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education (RP046B-15HTM). The NBCS has been supported by the Research Council of Norway grant 193387/V50 (to A.-L. Børresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A.-L. Børresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A.-L. Børresen-Dale and 27208 to V.N. Kristensen) and the Norwegian Cancer Society (to A.-L. Børresen-Dale and 419616 - 71248 - PR-2006-0282 to V.N. Kristensen). It has received funding from the K.G. Jebsen Centre for Breast Cancer Research (2012-2015). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC- BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manu- script does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, and U01 CA179715), and the North Carolina University Cancer Research Fund. The NGOBCS was supported by Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scienti fi c Research on Priority Areas, 17015049 and for Scienti fi c Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation, and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997- 1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI- NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/ A11699, C1275/C22524, C1275/A19187, C1275/A15956, and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scienti fi c development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME- ON) Network U19 CA148065. The SBCS was supported by Shef fi eld Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. The SCCS is supported by a grant from the National Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Of fi ce of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the of fi cial views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by Cancer Research UK [C490/A10124, C490/ A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the NUS start- up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425. The Sister Study (SIS- TER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TBCS was funded by The National Cancer Institute, Thailand. The TNBCC was supported by a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Bio- medical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The US3SS study was supported by Massachusetts (K.M.E., R01CA47305), Wisconsin (P.A.N., R01 CA47147) and New Hampshire (L.T.-E., R01CA69664) centers, and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WAABCS study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA89085 and P50 CA125183 and the D43 TW009112 grant), Susan G. Komen (SAC110026), the Dr. Ralph and Marian Falk Medical Research Trust, and the Avon Foundation for Women. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01. D.G.E. is supported by the all Manchester NIHR Biomedical research center Manchester (IS-BRC- 1215-20007). HUNBOCS, Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745, NKFI_OTKA K-112228. C.I. received support from the Nontherapeutic Subject Registry Shared Resource at George- town University (NIH/NCI P30-CA-51008) and the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. K.M. is supported by CRUK C18281/ A19169. City of Hope Clinical Cancer Community Research Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J Weitzel) from the National Cancer Institute and the of fi ce of the Directory, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the of fi cial views of the National Institutes of Health. The colorectal cancer genome-wide association analyses: Colorectal Transdisciplinary Study (CORECT): The content of this manuscript does not necessarily re fl ect the views or policies of the National Cancer Institute or any of the collaborating centers in the CORECT Consortium, nor does mention of trade names, commercial products or organizations imply endor- sement by the US Government or the CORECT Consortium. We are incredibly grateful for the contributions of Dr. Brian Henderson and Dr. Roger Green over the course of this study and acknowledge them in memoriam. We are also grateful for support from Daniel and Maryann Fong. ColoCare: we thank the many investigators and staff who made thisHHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN26 8201600004C. The head and neck cancer genome-wide association analyses: The study was supported by NIH/NCI: P50 CA097190, and P30 CA047904, Canadian Cancer Society Research Institute (no. 020214) and Cancer Care Ontario Research Chair to R.H. The Princess Margaret Hospital Head and Neck Cancer Translational Research Program is funded by the Wharton family, Joe ' s Team, Gordon Tozer, Bruce Galloway and the Elia family. Geoffrey Liu was supported by the Posluns Family Fund and the Lusi Wong Family Fund at the Princess Margaret Foundation, and the Alan B. Brown Chair in Molecular Genomics. This publication presents data from Head and Neck 5000 (H&N5000). H&N5000 was a component of independent research funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) in H&N5000 serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). National Cancer Institute (R01-CA90731); National Institute of Environmental Health Sciences (P30ES10126). The authors thank all the members of the GENCAPO team/The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). CPS-II recruitment and maintenance is supported with intramural research funding from the American Cancer Society. Genotyping per- formed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1 × 01HG007780- 0. The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/ 12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19-CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the Eur- opean Commission ' s 5th Framework Program (QLK1-2001-00182), the Italian Associa- tion for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to S.B., and Fon- dazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cienti fi ca y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). We thank Leticia Fernandez, Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba and Sergio and Rosalina Koifman, for their efforts with the IARC Latin America study São Paulo center. The IARC Central Europe study was supported by European Commission ' s INCO- COPERNICUS Program (IC15- CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is fi nancially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The lung cancer genome-wide association analyses: Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by (U19-CA148127, CA148127S1, U19CA203654, and Cancer Prevention Research Institute of Texas RR170048). The ILCCO data harmonization is supported by Cancer Care Ontario Research Chair of Population Studies to R. H. and Lunenfeld-Tanenbaum Research Institute, Sinai Health System. The TRICL-ILCCO OncoArray was supported by in-kind genotyping by the Centre for Inherited Disease Research (26820120008i-0-26800068-1). The CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03-0365, and FIS- 07-BI060604, FICYT/Asturias grant numbers FICYT PB02-67 and FICYT IB09-133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Pública. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health/National Cancer Insti- tute: UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989-01A1(PI Doherty). The Liverpool Lung project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578, CA074386. The Multi-ethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464, and CA148127. The work performed in MSH-PMH study was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. NJLCS was funded by the State Key Program of National Natural Science ofChina (81230067), the National Key Basic Research Program Grant (2011CB503805), the Major Program of the National Natural Science Foundation of China (81390543). The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The Shanghai Cohort Study (SCS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The Singapore Chinese Health Study (SCHS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997), and by a Cancer Center Support Grant (CCSG) at the H. Lee Mof fi tt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30- CA76292). The Vanderbilt Lung Cancer Study — BioVU dataset used for the analyses described was obtained from Vanderbilt University Medical Center ' s BioVU, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Vanderbilt CTSA grant UL1TR000445 from NCATS/NIH. Dr. Aldrich was supported by NIH/National Cancer Institute K07CA172294 (PI: Aldrich) and Dr. Bush was sup- ported by NHGRI/NIH U01HG004798 (PI: Crawford). The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The Kentucky Lung Cancer Research Initiative was supported by the Department of Defense [Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Com- mand Program] under award number: 10153006 (W81XWH-11-1-0781). Views and opinions of, and endorsements by the author(s) do not re fl ect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The M.D. Anderson Cancer Center study was supported in part by grants from the NIH (P50 CA070907, R01 CA176568) (to X.W.), Cancer Prevention & Research Institute of Texas (RP130502) (to X. W.), and The University of Texas MD Anderson Cancer Center institutional support for the Center for Translational and Public Health Genomics. The deCODE study of smoking and nicotine dependence was funded in part by a grant from NIDA (R01- DA017932). The study in Lodz center was partially funded by Nofer Institute of Occupational Med- icine, under task NIOM 10.13: Predictors of mortality from non-small cell lung cancer — fi eld study. Genetic sharing analysis was funded by NIH grant CA194393. The research undertaken by M.D.T., L.V.W., and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The work to assemble the FTND GWAS meta-analysis was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA) grant number R01 DA035825 (Prin- cipal Investigator [PI]: DBH). The study populations included COGEND (dbGaP phs000092.v1.p1 and phs000404.v1.p1), COPDGene (dbGaP phs000179.v3.p2), deCODE Genetics, EAGLE (dbGaP phs000093.vs.p2), and SAGE. dbGaP phs000092.v1.p1). See Hancock et al. Transl Psychiatry 2015 (PMCID: PMC4930126) for the full listing of funding sources and other acknowledgments. The Resource for the Study of Lung Cancer Epidemiology in North Trent (ReSoLuCENT)study was funded by the Shef fi eld Hospitals Charity, Shef fi eld Experimental Cancer Medicine Centre and Weston Park Hospital Cancer Charity. The ovarian cancer genome-wide association analysis: The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scienti fi c development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the U.S. National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.), and R01-CA058598 (M.T.G.); Canadian Institutes of Health Research (MOP-86727 (L.E.K.) and the Ovarian Cancer Research Fund (A.B.). The COGS project was funded through a European Commission ' s Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175) and through a grant from the U.S. National Insti- tutes of Health (R01-CA122443 (E.L.G)). Funding for individual studies: AAS: National Institutes of Health (RO1-CA142081); AOV: The Canadian Institutes for Health Research (MOP-86727); AUS: The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tas- mania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). The Australian Ovarian Cancer Study gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BAV: ELAN Funds of the University of Erlangen-Nuremberg; BEL: National Kankerplan; BGS: Breast Cancer Now, Institute of Cancer Research; BVU: Vanderbilt CTSA grant from the National Institutes of Health (NIH)/National Center for Advancing Translational SciencesNCATS) (ULTR000445); CAM: National Institutes of Health Research Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Cancer Centre; CHA: Innovative Research Team in University (PCSIRT) in China (IRT1076); CNI: Instituto de Salud Carlos III (PI12/01319); Ministerio de Economía y Competitividad (SAF2012); COE: Department of Defense (W81XWH-11-2-0131); CON: National Institutes of Health (R01-CA063678, R01-CA074850; and R01-CA080742); DKE: Ovarian Cancer Research Fund; DOV: National Institutes of Health R01-CA112523 and R01-CA87538; EMC: Dutch Cancer Society (EMC 2014-6699); EPC: The coordination of EPIC is fi nancially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l ' Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC- Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom); GER: German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401) and the German Cancer Research Center (DKFZ); GRC: This research has been co- fi nanced by the European Union (European Social Fund — ESF) and Greek national funds through the Operational Program " Education and Lifelong Learn- ing " of the National Strategic Reference Framework (NSRF) — Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund; GRR: Roswell Park Cancer Institute Alliance Foundation, P30 CA016056; HAW: U.S. National Institutes of Health (R01- CA58598, N01-CN-55424, and N01-PC-67001); HJO: Intramural funding; Rudolf- Bartling Foundation; HMO: Intramural funding; Rudolf-Bartling Foundation; HOC: Helsinki University Research Fund; HOP: Department of Defense (DAMD17-02-1-0669) and NCI (K07-CA080668, R01-CA95023, P50-CA159981 MO1-RR000056 R01- CA126841); HUO: Intramural funding; Rudolf-Bartling Foundation; JGO: JSPS KAKENHI grant; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; KRA: This study (Ko-EVE) was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); LAX: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; LUN: ERC-2011-AdG 294576-risk factors cancer, Swedish Cancer Society, Swedish Research Council, Beta Kamprad Foundation; MAC: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Fraternal Order of Eagles; MAL: Funding for this study was provided by research grant R01- CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mer- maid I project; MAS: Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; MAY: National Institutes of Health (R01- CA122443, P30-CA15083, and P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; MCC: Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC) grants number 209057, 251533, 396414, and 504715; MDA: DOD Ovarian Cancer Research Program (W81XWH-07-0449); MEC: NIH (CA54281, CA164973, CA63464); MOF: Mof fi tt Cancer Center, Merck Pharmaceuticals, the state of Florida, Hillsborough County, and the city of Tampa; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of Health R01- CA54419 and P50-CA105009 and Department of Defense W81XWH-10-1-02802; NHS: UM1 CA186107, P01 CA87969, R01 CA49449, R01-CA67262, UM1 CA176726; NJO: National Cancer Institute (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, and P30-CA072720) and the Cancer Institute of New Jersey; If Sara Olson and/or Irene Orlow is a co-author, please add NCI CCSG award (P30-CA008748) to the funding sources; NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; NTH: Radboud University Medical Centre; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142) and Brisbane Women ' s Club; ORE: OHSU Foundation; OVA: This work was supported by Canadian Institutes of Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1; PLC: Intramural Research Program of the National Cancer Institute; POC: Pomeranian Medical Uni- versity; POL: Intramural Research Program of the National Cancer Institute; PVD: Canadian Cancer Society and Cancer Research Society GRePEC Program; RBH: National Health and Medical Research Council of Australia; RMH: Cancer Research UK, Royal Marsden Hospital; RPC: National Institute of Health (P50-CA159981, R01-CA126841); SEA: Cancer Research UK (C490/A10119 C490/A10124); UK National Institute forHealth Research Biomedical Research Centres at the University of Cambridge; SIS: NIH, National Institute of Environmental Health Sciences, Z01-ES044005 and Z01-ES049033; SMC: The bbSwedish Research Council-SIMPLER infrastructure; the Swedish Cancer Foundation; SON: National Health Research and Development Program, Health Canada, grant 6613-1415-53; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); STA: NIH grants U01 CA71966 and U01 CA69417; SWE: Swedish Cancer foundation, WeCanCureCancer and VårKampMotCancer foundation; SWH: NIH (NCI) grant R37-CA070867; TBO: National Institutes of Health (R01-CA106414-A2), American Cancer Society (CRTG-00-196-01- CCE), Department of Defense (DAMD17-98-1-8659), Celma Mastery Ovarian Cancer Foundation; TOR: NIH grants R01-CA063678 and R01 CA063682; UCI: NIH R01- CA058860 and the Lon V Smith Foundation grant LVS39420; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre; UKR: Cancer Research UK (C490/A6187), UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; USC: P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403, and Cali- fornia Cancer Research Program (00-01389V-20170, 2II0200); VAN: BC Cancer Foun- dation, VGH & UBC Hospital Foundation; VTL: NIH K05-CA154337; WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 & ID 628903. Cancer Institute NSW Grants 12/RIG/1-17 & 15/RIG/1-16; WOC: National Science Centren (N N301 5645 40). The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academia Reserve. The prostate cancer genome-wide association analyses: we pay tribute to Brian Henderson, who was a driving force behind the OncoArray project, for his vision and leadership, and who sadly passed away before seeing its fruition. We also thank the individuals who participated in these studies enabling this work. The ELLIPSE/ PRACTICAL (http//:practical.icr.ac.uk) prostate cancer consortium and his collaborating partners were supported by multiple funding mechanisms enabling this current work. ELLIPSE/PRACTICAL Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) (U19 CA148537 for ELucidating Loci Involved in Prostate Cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I). Additional analytical support was provided by NIH NCI U01 CA188392 (F.R.S.). Funding for the iCOGS infrastructure came from the European Community ' s Seventh Framework Pro- gramme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/ A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112; the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This work was supported by the Canadian Institutes of Health Research, European Commission ' s Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/ A3354, C5047/A10692, C16913/A6135, C5047/A21332 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA148537-01 (the GAME-ON initiative). We also thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Founda- tion, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, and The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. The Prostate Cancer Program of Cancer Council Victoria also acknowledge grant support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, and 614296), VicHealth, Cancer Council Victoria, The Prostate Cancer Foun- dation of Australia, The Whitten Foundation, PricewaterhouseCoopers, and Tattersall ' s. E.A.O., D.M.K., and E.M.K. acknowledge the Intramural Program of the National Human Genome Research Institute for their support. The BPC3 was supported by the U.S. National Institutes of Health, National Cancer Institute (cooperative agreements U01- CA98233 to D.J.H., U01-CA98710 to S.M.G., U01-CA98216 to E.R., and U01-CA98758 to B.E.H., and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). CAPS GWAS study was supported by the Swedish Cancer Foundation (grant no 09-0677, 11-484, 12-823), the Cancer Risk Prediction Center (CRisP; www.crispcenter.org ), a Linneus Centre (Contract ID 70867902) fi nanced by the Swedish Research Council, Swedish Research Council (grant no K2010-70 × - 20430-04-3, 2014-2269). The Hannover Prostate Cancer Study was supported by the Lower Saxonian Cancer Society. PEGASUS was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. RAPPER was supported by the NIHR Manchester Bio- medical Research Center, Cancer Research UK (C147/A25254, C1094/A18504) and the EUs7Framework Programme Grant/Agreement no 60186. Overall: this research has been conducted using the UK Biobank Resource (application number 16549). NHS is supported by UM1 CA186107 (NHS cohort infrastructure grant), P01 CA87969, and R01 CA49449. NHSII is supported by UM1 CA176726 (NHSII cohort infrastructure grant),and R01-CA67262. A.L.K. is supported by R01 MH107649. We would like to thank the participants and staff of the NHS and NHSII for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. ; Sí

COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT ; COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220* ; Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group. ; French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D'Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France. ; CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children's Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France. ; Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium. ; COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O'Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d'Immunologie Clinique, d'Inflammation et d'Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children's Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children's Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children's Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome "Tor Vergata," Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d'Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort. ; NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. ; Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection. ; We thank the generous donation from Fisher Center for Alzheimer's Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project "Risposta immune in pazienti con COVID-19 e co-morbidità"), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by "Integrative Biology of Emerging Infectious Diseases" (grant no. ANR-10-LABX-62-IBEID), the "Fondation pour la Recherche Medicale" (grant FRM - EQU202003010193), the "Agence Nationale de la Recherche" (ANR FLASH COVID project IDISCOVR cofounded by the "Fondation pour la Recherche Médicale"), University of Paris ("Plan de Soutien Covid-19": RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by "Agence Nationale de la Recherche" (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris "PLAN D'URGENCE COVID19". LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and "Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19"). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine ; Peer reviewed

Publisher's version (útgefin grein). ; Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis. ; The authors in this manuscript were working on behalf of BCAC, CCFR, CIMBA, CORECT, GECCO, OCAC, PRACTICAL, CRUK, BPC3, CAPS, PEGASUS, TRICL-ILCCO, ABCTB, APCB, BCFR, CONSIT TEAM, EMBRACE, GC-HBOC, GEMO, HEBON, kConFab/AOCS Mod SQuaD, and SWE-BRCA. The breast cancer genome-wide association analyses: BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST, respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministère de l'Économie, Science et Innovation du Québec through Genome Québec and the PSR-SIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112—the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia), and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The ACP study is funded by the Breast Cancer Research Trust, UK. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR-NY, BCFR-PA, and BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. BOCS is supported by funds from Cancer Research UK (C8620/A8372/A15106) and the Institute of Cancer Research (UK). BOCS acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) (SALUD-2002-C01-7462). Sample collection and processing was funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI11/00923 and PI12/00070). COLBCCC is supported by the German Cancer Research Center (DKFZ), Heidelberg, Germany. D.T. was in part supported by a postdoctoral fellowship from the Alexander von Humboldt Foundation. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. H.A.C eceives support from the Lon V Smith Foundation (LVS39420). The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, and 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). GLACIER was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf-Bartling Foundation. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan, by National Cancer Center Research and Development Fund, and "Practical Research for Innovative Cancer Control (15ck0106177h0001)" from Japan Agency for Medical Research and development, AMED, and Cancer Bio Bank Aichi. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014, and 17-44-020498. ICICLE was supported by Breast Cancer Now, CRUK, and Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (A.L.F.) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (E.V.O.) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.-T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. The KOHBRA study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. L.M.B.C. is supported by the 'Stichting tegen Kanker'. D.L. is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov" and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 × 1000"). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839, and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286, and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701. MYBRCA is funded by research grants from the Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education (RP046B-15HTM). The NBCS has been supported by the Research Council of Norway grant 193387/V50 (to A.-L. Børresen-Dale and V.N. Kristensen) and grant 193387/H10 (to A.-L. Børresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A.-L. Børresen-Dale and 27208 to V.N. Kristensen) and the Norwegian Cancer Society (to A.-L. Børresen-Dale and 419616 - 71248 - PR-2006-0282 to V.N. Kristensen). It has received funding from the K.G. Jebsen Centre for Breast Cancer Research (2012-2015). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, and U01 CA179715), and the North Carolina University Cancer Research Fund. The NGOBCS was supported by Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas, 17015049 and for Scientific Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation, and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956, and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network U19 CA148065. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. The SCCS is supported by a grant from the National Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TBCS was funded by The National Cancer Institute, Thailand. The TNBCC was supported by a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The US3SS study was supported by Massachusetts (K.M.E., R01CA47305), Wisconsin (P.A.N., R01 CA47147) and New Hampshire (L.T.-E., R01CA69664) centers, and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WAABCS study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA89085 and P50 CA125183 and the D43 TW009112 grant), Susan G. Komen (SAC110026), the Dr. Ralph and Marian Falk Medical Research Trust, and the Avon Foundation for Women. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01. D.G.E. is supported by the all Manchester NIHR Biomedical research center Manchester (IS-BRC-1215-20007). HUNBOCS, Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grant KTIA-OTKA CK-80745, NKFI_OTKA K-112228. C.I. received support from the Nontherapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI P30-CA-51008) and the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. K.M. is supported by CRUK C18281/A19169. City of Hope Clinical Cancer Community Research Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J Weitzel) from the National Cancer Institute and the office of the Directory, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The colorectal cancer genome-wide association analyses: Colorectal Transdisciplinary Study (CORECT): The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CORECT Consortium, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the CORECT Consortium. We are incredibly grateful for the contributions of Dr. Brian Henderson and Dr. Roger Green over the course of this study and acknowledge them in memoriam. We are also grateful for support from Daniel and Maryann Fong. ColoCare: we thank the many investigators and staff who made this research possible in ColoCare Seattle and ColoCare Heidelberg. ColoCare was initiated and developed at the Fred Hutchinson Cancer Research Center by Drs. Ulrich and Grady. CCFR: the Colon CFR graciously thanks the generous contributions of their study participants, dedication of study staff, and financial support from the U.S. National Cancer Institute, without which this important registry would not exist. Galeon: GALEON wishes to thank the Department of Surgery of University Hospital of Santiago (CHUS), Sara Miranda Ponte, Carmen M Redondo, and the staff of the Department of Pathology and Biobank of CHUS, Instituto de Investigación Sanitaria de Santiago (IDIS), Instituto de Investigación Sanitaria Galicia Sur (IISGS), SERGAS, Vigo, Spain, and Programa Grupos Emergentes, Cancer Genetics Unit, CHUVI Vigo Hospital, Instituto de Salud Carlos III, Spain. MCCS: this study was made possible by the contribution of many people, including the original investigators and the diligent team who recruited participants and continue to work on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who took part in the study and provided blood samples. SEARCH: We acknowledge the contributions of Mitul Shah, Val Rhenius, Sue Irvine, Craig Luccarini, Patricia Harrington, Don Conroy, Rebecca Mayes, and Caroline Baynes. The Swedish low-risk colorectal cancer study: we thank Berith Wejderot and the Swedish low-risk colorectal cancer study group. Genetics & Epidemiology of Colorectal Cancer Consortium (GECCO): we thank all those at the GECCO Coordinating Center for helping bring together the data and people that made this project possible. ASTERISK: we are very grateful to Dr. Bruno Buecher without whom this project would not have existed. We also thank all those who agreed to participate in this study, including the patients and the healthy control persons, as well as all the physicians, technicians and students. DACHS: we thank all participants and cooperating clinicians, and Ute Handte-Daub, Renate Hettler-Jensen, Utz Benscheid, Muhabbet Celik, and Ursula Eilber for excellent technical assistance. HPFS, NHS and PHS: we acknowledge Patrice Soule and Hardeep Ranu of the Dana-Farber Harvard Cancer Center High-Throughput Polymorphism Core who assisted in the genotyping for NHS, HPFS, and PHS under the supervision of Dr. Immaculata Devivo and Dr. David Hunter, Qin (Carolyn) Guo, and Lixue Zhu who assisted in programming for NHS and HPFS and Haiyan Zhang who assisted in programming for the PHS. We thank the participants and staff of the Nurses' Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: A.L., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I.L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., W.Y. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Certain data used in this publication were obtained from the DPH. We assume full responsibility for analyses and interpretation of these data. PLCO: we thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff or the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services Inc., Ms. Barbara O'Brien and staff, Westat Inc. and Drs. Bill Kopp, Wen Shao and staff, SAIC-Frederick. Most importantly, we acknowledge the study participants for their contributions for making this study possible. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI. PMH: we thank the study participants and staff of the Hormones and Colon Cancer study. WHI: we thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://cleo.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short20List.pdf. CORECT: The CORECT Study was supported by the National Cancer Institute, National Institutes of Health (NCI/NIH), U.S. Department of Health and Human Services (grant numbers U19 CA148107, R01 CA81488, P30 CA014089, R01 CA197350; P01 CA196569; and R01 CA201407) and National Institutes of Environmental Health Sciences, National Institutes of Health (grant number T32 ES013678). The ATBC Study was supported by the US Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C) from the National Cancer Institute. The Cancer Prevention Study-II Nutrition Cohort is funded by the American Cancer Society. ColoCare: This work was supported by the National Institutes of Health (grant numbers R01 CA189184, U01 CA206110, 2P30CA015704-40 (Gilliland)), the Matthias Lackas-Foundation, the German Consortium for Translational Cancer Research, and the EU TRANSCAN initiative. Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): funding for GECCO was provided by the National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (grant numbers U01 CA137088, R01 CA059045, and U01 CA164930). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. The Colon Cancer Family Registry (CFR) Illumina GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (grant numbers U01 CA122839, R01 CA143247). The Colon CFR/CORECT Affymetrix Axiom GWAS and OncoArray GWAS were supported by funding from National Cancer Institute, National Institutes of Health (grant number U19 CA148107 to S.G.). The Colon CFR participant recruitment and collection of data and biospecimens used in this study were supported by the National Cancer Institute, National Institutes of Health (grant number UM1 CA167551) and through cooperative agreements with the following Colon CFR centers: Australasian Colorectal Cancer Family Registry (NCI/NIH grant numbers U01 CA074778 and U01/U24 CA097735), USC Consortium Colorectal Cancer Family Registry (NCI/NIH grant numbers U01/U24 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH grant number U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (NCI/NIH grant number U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (NCI/NIH grant number U01/U24 CA074794), and University of Hawaii Colorectal Cancer Family Registry (NCI/NIH grant number U01/U24 CA074806), Additional support for case ascertainment was provided from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute to Fred Hutchinson Cancer Research Center (Control Nos. N01-CN-67009 and N01-PC-35142, and Contract No. HHSN2612013000121), the Hawai'i Department of Health (Control Nos. N01-PC-67001 and N01-PC-35137, and Contract No. HHSN26120100037C, and the California Department of Public Health (contracts HHSN261201000035C awarded to the University of Southern California, and the following state cancer registries: A.Z., C.O., M.N., N.C., N.H., and by the Victoria Cancer Registry and Ontario Cancer Registry. ESTHER/VERDI was supported by grants from the Baden–Württemberg Ministry of Science, Research and Arts and the German Cancer Aid. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. GALEON: FIS Intrasalud (PI13/01136). The MCCS was further supported by Australian NHMRC grants 509348, 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database. MSKCC: the work at Sloan Kettering in New York was supported by the Robert and Kate Niehaus Center for Inherited Cancer Genomics and the Romeo Milio Foundation. Moffitt: This work was supported by funding from the National Institutes of Health (grant numbers R01 CA189184, P30 CA076292), Florida Department of Health Bankhead-Coley Grant 09BN-13, and the University of South Florida Oehler Foundation. Moffitt contributions were supported in part by the Total Cancer Care Initiative, Collaborative Data Services Core, and Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a National Cancer Institute-designated Comprehensive Cancer Center (grant number P30 CA076292). SEARCH: Cancer Research UK (C490/A16561). The Spanish study was supported by Instituto de Salud Carlos III, co-funded by FEDER funds –a way to build Europe– (grants PI14-613 and PI09-1286), Catalan Government DURSI (grant 2014SGR647), and Junta de Castilla y León (grant LE22A10-2). The Swedish Low-risk Colorectal Cancer Study: the study was supported by grants from the Swedish research council; K2015-55 × -22674-01-4, K2008-55 × -20157-03-3, K2006-72 × -20157-01-2 and the Stockholm County Council (ALF project). CIDR genotyping for the Oncoarray was conducted under contract 268201200008I (to K.D.), through grant 101HG007491-01 (to C.I.A.). The Norris Cotton Cancer Center - P30CA023108, The Quantitative Biology Research Institute - P20GM103534, and the Coordinating Center for Screen Detected Lesions - U01CA196386 also supported efforts of C.I.A. This work was also supported by the National Cancer Institute (grant numbers U01 CA1817700, R01 CA144040). ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue Régionale Contre le Cancer (LRCC). COLO2&3: National Institutes of Health (grant number R01 CA060987). DACHS: This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1, and BR 1704/17-1), the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany, and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A, and 01ER1505B). DALS: National Institutes of Health (grant number R01 CA048998 to M.L.S). HPFS is supported by National Institutes of Health (grant numbers P01 CA055075, UM1 CA167552, R01 137178, and P50 CA127003), NHS by the National Institutes of Health (grant numbers UM1 CA186107, R01 CA137178, P01 CA087969, and P50 CA127003), NHSII by the National Institutes of Health (grant numbers R01 050385CA and UM1 CA176726), and PHS by the National Institutes of Health (grant number R01 CA042182). MEC: National Institutes of Health (grant numbers R37 CA054281, P01 CA033619, and R01 CA063464). OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (grant number U01 CA074783); see Colon CFR section above. As subset of ARCTIC, OFCCR is supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. T.J.H. and B.W.Z. are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples was genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS, Colon CGEMS pancreatic cancer scan (PanScan), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, 23 and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (grant number R01 CA076366). VITAL: National Institutes of Health (grant number K05-CA154337). WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The head and neck cancer genome-wide association analyses: The study was supported by NIH/NCI: P50 CA097190, and P30 CA047904, Canadian Cancer Society Research Institute (no. 020214) and Cancer Care Ontario Research Chair to R.H. The Princess Margaret Hospital Head and Neck Cancer Translational Research Program is funded by the Wharton family, Joe's Team, Gordon Tozer, Bruce Galloway and the Elia family. Geoffrey Liu was supported by the Posluns Family Fund and the Lusi Wong Family Fund at the Princess Margaret Foundation, and the Alan B. Brown Chair in Molecular Genomics. This publication presents data from Head and Neck 5000 (H&N5000). H&N5000 was a component of independent research funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Human papillomavirus (HPV) in H&N5000 serology was supported by a Cancer Research UK Programme Grant, the Integrative Cancer Epidemiology Programme (grant number: C18281/A19169). National Cancer Institute (R01-CA90731); National Institute of Environmental Health Sciences (P30ES10126). The authors thank all the members of the GENCAPO team/The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). CPS-II recruitment and maintenance is supported with intramural research funding from the American Cancer Society. Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1 × 01HG007780-0. The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19-CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission's 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222). The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to S.B., and Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). We thank Leticia Fernandez, Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba and Sergio and Rosalina Koifman, for their efforts with the IARC Latin America study São Paulo center. The IARC Central Europe study was supported by European Commission's INCO-COPERNICUS Program (IC15- CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28. The IARC Oral Cancer Multicenter study was funded by grant S06 96 202489 05F02 from Europe against Cancer; grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The lung cancer genome-wide association analyses: Transdisciplinary Research for Cancer in Lung (TRICL) of the International Lung Cancer Consortium (ILCCO) was supported by (U19-CA148127, CA148127S1, U19CA203654, and Cancer Prevention Research Institute of Texas RR170048). The ILCCO data harmonization is supported by Cancer Care Ontario Research Chair of Population Studies to R. H. and Lunenfeld-Tanenbaum Research Institute, Sinai Health System. The TRICL-ILCCO OncoArray was supported by in-kind genotyping by the Centre for Inherited Disease Research (26820120008i-0-26800068-1). The CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03-0365, and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02-67 and FICYT IB09-133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiologia y Salud Pública. CIBERESP, SPAIN. The work performed in the CARET study was supported by the National Institute of Health/National Cancer Institute: UM1 CA167462 (PI: Goodman), National Institute of Health UO1-CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA151989-01A1(PI Doherty). The Liverpool Lung project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578, CA074386. The Multi-ethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464, and CA148127. The work performed in MSH-PMH study was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to R.J.H. and G.L. and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. NJLCS was funded by the State Key Program of National Natural Science of China (81230067), the National Key Basic Research Program Grant (2011CB503805), the Major Program of the National Natural Science Foundation of China (81390543). The Norway study was supported by Norwegian Cancer Society, Norwegian Research Council. The Shanghai Cohort Study (SCS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The Singapore Chinese Health Study (SCHS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The work in TLC study has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997), and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The Vanderbilt Lung Cancer Study—BioVU dataset used for the analyses described was obtained from Vanderbilt University Medical Center's BioVU, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Vanderbilt CTSA grant UL1TR000445 from NCATS/NIH. Dr. Aldrich was supported by NIH/National Cancer Institute K07CA172294 (PI: Aldrich) and Dr. Bush was supported by NHGRI/NIH U01HG004798 (PI: Crawford). The Copenhagen General Population Study (CGPS) was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The Kentucky Lung Cancer Research Initiative was supported by the Department of Defense [Congressionally Directed Medical Research Program, U.S. Army Medical Research and Materiel Command Program] under award number: 10153006 (W81XWH-11-1-0781). Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense. This research was also supported by unrestricted infrastructure funds from the UK Center for Clinical and Translational Science, NIH grant UL1TR000117 and Markey Cancer Center NCI Cancer Center Support Grant (P30 CA177558) Shared Resource Facilities: Cancer Research Informatics, Biospecimen and Tissue Procurement, and Biostatistics and Bioinformatics. The M.D. Anderson Cancer Center study was supported in part by grants from the NIH (P50 CA070907, R01 CA176568) (to X.W.), Cancer Prevention & Research Institute of Texas (RP130502) (to X.W.), and The University of Texas MD Anderson Cancer Center institutional support for the Center for Translational and Public Health Genomics. The deCODE study of smoking and nicotine dependence was funded in part by a grant from NIDA (R01- DA017932). The study in Lodz center was partially funded by Nofer Institute of Occupational Medicine, under task NIOM 10.13: Predictors of mortality from non-small cell lung cancer—field study. Genetic sharing analysis was funded by NIH grant CA194393. The research undertaken by M.D.T., L.V.W., and M.S.A. was partly funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.D.T. holds a Medical Research Council Senior Clinical Fellowship (G0902313). The work to assemble the FTND GWAS meta-analysis was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA) grant number R01 DA035825 (Principal Investigator [PI]: DBH). The study populations included COGEND (dbGaP phs000092.v1.p1 and phs000404.v1.p1), COPDGene (dbGaP phs000179.v3.p2), deCODE Genetics, EAGLE (dbGaP phs000093.vs.p2), and SAGE. dbGaP phs000092.v1.p1). See Hancock et al. Transl Psychiatry 2015 (PMCID: PMC4930126) for the full listing of funding sources and other acknowledgments. The Resource for the Study of Lung Cancer Epidemiology in North Trent (ReSoLuCENT)study was funded by the Sheffield Hospitals Charity, Sheffield Experimental Cancer Medicine Centre and Weston Park Hospital Cancer Charity. The ovarian cancer genome-wide association analysis: The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the U.S. National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.), and R01-CA058598 (M.T.G.); Canadian Institutes of Health Research (MOP-86727 (L.E.K.) and the Ovarian Cancer Research Fund (A.B.). The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175) and through a grant from the U.S. National Institutes of Health (R01-CA122443 (E.L.G)). Funding for individual studies: AAS: National Institutes of Health (RO1-CA142081); AOV: The Canadian Institutes for Health Research (MOP-86727); AUS: The Australian Ovarian Cancer Study Group was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). The Australian Ovarian Cancer Study gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BAV: ELAN Funds of the University of Erlangen-Nuremberg; BEL: National Kankerplan; BGS: Breast Cancer Now, Institute of Cancer Research; BVU: Vanderbilt CTSA grant from the National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) (ULTR000445); CAM: National Institutes of Health Research Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Cancer Centre; CHA: Innovative Research Team in University (PCSIRT) in China (IRT1076); CNI: Instituto de Salud Carlos III (PI12/01319); Ministerio de Economía y Competitividad (SAF2012); COE: Department of Defense (W81XWH-11-2-0131); CON: National Institutes of Health (R01-CA063678, R01-CA074850; and R01-CA080742); DKE: Ovarian Cancer Research Fund; DOV: National Institutes of Health R01-CA112523 and R01-CA87538; EMC: Dutch Cancer Society (EMC 2014-6699); EPC: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom); GER: German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (01 GB 9401) and the German Cancer Research Center (DKFZ); GRC: This research has been co-financed by the European Union (European Social Fund—ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)—Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund; GRR: Roswell Park Cancer Institute Alliance Foundation, P30 CA016056; HAW: U.S. National Institutes of Health (R01-CA58598, N01-CN-55424, and N01-PC-67001); HJO: Intramural funding; Rudolf-Bartling Foundation; HMO: Intramural funding; Rudolf-Bartling Foundation; HOC: Helsinki University Research Fund; HOP: Department of Defense (DAMD17-02-1-0669) and NCI (K07-CA080668, R01-CA95023, P50-CA159981 MO1-RR000056 R01-CA126841); HUO: Intramural funding; Rudolf-Bartling Foundation; JGO: JSPS KAKENHI grant; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; KRA: This study (Ko-EVE) was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 0920010); LAX: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; LUN: ERC-2011-AdG 294576-risk factors cancer, Swedish Cancer Society, Swedish Research Council, Beta Kamprad Foundation; MAC: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; Fraternal Order of Eagles; MAL: Funding for this study was provided by research grant R01- CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project; MAS: Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; MAY: National Institutes of Health (R01-CA122443, P30-CA15083, and P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; MCC: Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC) grants number 209057, 251533, 396414, and 504715; MDA: DOD Ovarian Cancer Research Program (W81XWH-07-0449); MEC: NIH (CA54281, CA164973, CA63464); MOF: Moffitt Cancer Center, Merck Pharmaceuticals, the state of Florida, Hillsborough County, and the city of Tampa; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of Health R01-CA54419 and P50-CA105009 and Department of Defense W81XWH-10-1-02802; NHS: UM1 CA186107, P01 CA87969, R01 CA49449, R01-CA67262, UM1 CA176726; NJO: National Cancer Institute (NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, and P30-CA072720) and the Cancer Institute of New Jersey; If Sara Olson and/or Irene Orlow is a co-author, please add NCI CCSG award (P30-CA008748) to the funding sources; NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; NTH: Radboud University Medical Centre; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142) and Brisbane Women's Club; ORE: OHSU Foundation; OVA: This work was supported by Canadian Institutes of Health Research grant (MOP-86727) and by NIH/NCI 1 R01CA160669-01A1; PLC: Intramural Research Program of the National Cancer Institute; POC: Pomeranian Medical University; POL: Intramural Research Program of the National Cancer Institute; PVD: Canadian Cancer Society and Cancer Research Society GRePEC Program; RBH: National Health and Medical Research Council of Australia; RMH: Cancer Research UK, Royal Marsden Hospital; RPC: National Institute of Health (P50-CA159981, R01-CA126841); SEA: Cancer Research UK (C490/A10119 C490/A10124); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; SIS: NIH, National Institute of Environmental Health Sciences, Z01-ES044005 and Z01-ES049033; SMC: The bbSwedish Research Council-SIMPLER infrastructure; the Swedish Cancer Foundation; SON: National Health Research and Development Program, Health Canada, grant 6613-1415-53; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); STA: NIH grants U01 CA71966 and U01 CA69417; SWE: Swedish Cancer foundation, WeCanCureCancer and VårKampMotCancer foundation; SWH: NIH (NCI) grant R37-CA070867; TBO: National Institutes of Health (R01-CA106414-A2), American Cancer Society (CRTG-00-196-01-CCE), Department of Defense (DAMD17-98-1-8659), Celma Mastery Ovarian Cancer Foundation; TOR: NIH grants R01-CA063678 and R01 CA063682; UCI: NIH R01-CA058860 and the Lon V Smith Foundation grant LVS39420; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre; UKR: Cancer Research UK (C490/A6187), UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; USC: P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403, and California Cancer Research Program (00-01389V-20170, 2II0200); VAN: BC Cancer Foundation, VGH & UBC Hospital Foundation; VTL: NIH K05-CA154337; WMH: National Health and Medical Research Council of Australia, Enabling Grants ID 310670 & ID 628903. Cancer Institute NSW Grants 12/RIG/1-17 & 15/RIG/1-16; WOC: National Science Centren (N N301 5645 40). The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academia Reserve. The prostate cancer genome-wide association analyses: we pay tribute to Brian Henderson, who was a driving force behind the OncoArray project, for his vision and leadership, and who sadly passed away before seeing its fruition. We also thank the individuals who participated in these studies enabling this work. The ELLIPSE/PRACTICAL (http//:practical.icr.ac.uk) prostate cancer consortium and his collaborating partners were supported by multiple funding mechanisms enabling this current work. ELLIPSE/PRACTICAL Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) (U19 CA148537 for ELucidating Loci Involved in Prostate Cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I). Additional analytical support was provided by NIH NCI U01 CA188392 (F.R.S.). Funding for the iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112; the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This work was supported by the Canadian Institutes of Health Research, European Commission's Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, C5047/A21332 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA148537-01 (the GAME-ON initiative). We also thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, and The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. The Prostate Cancer Program of Cancer Council Victoria also acknowledge grant support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, and 614296), VicHealth, Cancer Council Victoria, The Prostate Cancer Foundation of Australia, The Whitten Foundation, PricewaterhouseCoopers, and Tattersall's. E.A.O., D.M.K., and E.M.K. acknowledge the Intramural Program of the National Human Genome Research Institute for their support. The BPC3 was supported by the U.S. National Institutes of Health, National Cancer Institute (cooperative agreements U01-CA98233 to D.J.H., U01-CA98710 to S.M.G., U01-CA98216 to E.R., and U01-CA98758 to B.E.H., and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). CAPS GWAS study was supported by the Swedish Cancer Foundation (grant no 09-0677, 11-484, 12-823), the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linneus Centre (Contract ID 70867902) financed by the Swedish Research Council, Swedish Research Council (grant no K2010-70 × -20430-04-3, 2014-2269). The Hannover Prostate Cancer Study was supported by the Lower Saxonian Cancer Society. PEGASUS was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. RAPPER was supported by the NIHR Manchester Biomedical Research Center, Cancer Research UK (C147/A25254, C1094/A18504) and the EU's 7th Framework Programme Grant/Agreement no 60186. Overall: this research has been conducted using the UK Biobank Resource (application number 16549). NHS is supported by UM1 CA186107 (NHS cohort infrastructure grant), P01 CA87969, and R01 CA49449. NHSII is supported by UM1 CA176726 (NHSII cohort infrastructure grant), and R01-CA67262. A.L.K. is supported by R01 MH107649. We would like to thank the participants and staff of the NHS and NHSII for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. ; Peer Reviewed