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Open Access#8412016

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J; Li, Qiyuan; Delgado, Melissa K; Lee, Janet M; Aittomaki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Bandera, Elisa V; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Matthias W; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Ahmad Buhari, Shaik; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M; Cook, Linda S; Cox, Angela; Cramer, Daniel W; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Doerk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Engel, Christoph; Lee, Eunjung; Gareth Evans, D; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fridley, Brooke L; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A; Garber, Judy; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G; Glasspool, Rosalind; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; Gonzalez-Neira, Anna; Goode, Ellen L; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Guenel, Pascal; Haiman, Christopher A; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O; Harrington, Patricia A; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Heitz, Florian; Herzog, Josef; Hogdall, Estrid; Hogdall, Claus K; Hogervorst, Frans B. L; Hollestelle, Antoinette; Hopper, John L; Hulick, Peter J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y; Khan, Sofia; Kiemeney, Lambertus A; Kruger Kjaer, Susanne; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R; Milne, Roger L; Montagna, Marco; Moysich, Kirsten B; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; OMalley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Kyung Park, Sue; Pearce, Celeste L; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poole, Elizabeth M; Pylkas, Katri; Radice, Paolo; Rantala, Johanna; Usman Rashid, Muhammad; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A; Rodriguez, Gus; Anne Rossing, Mary; Rudolph, Anja; Salvesen, Helga B; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Sellers, Thomas A; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F; Sinilnikova, Olga M; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stenmark Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Kathryn L; Beth Terry, Mary; Thomassen, Mads; Grazia Tibiletti, Maria; Tihomirova, Laima; Tognazzo, Silvia; Ewart Toland, Amanda; Tomlinson, Ian; Torres, Diana; Truong, Therese; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S; Vachon, Celine; van den Ouweland, Ans M. W; van Doorn, Helena C; van Rensburg, Elizabeth J; Vant Veer, Laura J; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Wildiers, Hans; Winqvist, Robert; Wu, Anna H; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Kum Khanna, Kum; Simard, Jacques; Monteiro, Alvaro N; French, Juliet D; Couch, Fergus J; Freedman, Matthew L; Easton, Douglas F; Dunning, Alison M; Pharoah, Paul D; Edwards, Stacey L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Gayther, Simon A

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Open Access#8422012

Report on Italian libraries ; Rapporto sulle biblioteche italiane 2001

Ponzani, Vittorio

IntroductionThe Report that the AIB has decided to publish starting from this year aims at presenting, even if synthetically, the main characteristics of an overview of Italian libraries, each time pointing out the questions, tendencies and some of the events that are of most interest to those who are interested in the development of the library service in our country.When it is proposed to describe a national picture of the situation of the libraries of the various types (public, university, state, scholastic, ecclesiastic, private, etc.) one finds oneself before the almost total absence of comparable and trustworthy organic information. Using the various sources available, it is possible to estimate with a certain approximation that the over 15,000 Italian libraries (in which approximately 20,000 people work) possess almost 200 million documents, that they acquire annually almost 7 million books, that their annual users are little less than 10 million and the loans made are around 65 million. It is believed that in the year 2001 the running costs exceeded 1000 billion lire, of which a little more than 10% were destined to the purchase of documents.LegislationThe year 2001 was rich in new details with regard to the sector of legislation for libraries. This was also due to the effect of the constitutional reforms and the new scenarios relative to the responsibilities and federalist arrangement of the State.Regulations of particular importance for libraries and indirectly linked to the overall institutional situation are those contained in the law of 28 December 2001, no. 448 (finance law 2002). This prescribes that the management of services aimed at the improvement of the public use and development of the artistic patrimony (and therefore also of the state libraries) can be entrusted to subjects other than those of the state. It also introduces an art. 113 bis in the sole text of the laws on the organization of local bodies (legislative decree 18 August 2000, no. 267), on the basis of which "local public services without industrial importance are managed through direct entrusting to: a) institutions; b) special businesses, including consortiums; c) joint-stock companies" and only as a residual solution (paragraph 2) "is economic management permitted when, due to the small dimensions or the characteristics of the service, it is not opportune to proceed to entrusting it to subjects as described in paragraph 1". Awaited on many sides as the chance to respond to a number of the age-old problems that have afflicted the sector of state public libraries for decades, the new organization regulations of the Ministry for cultural and artistic heritage, issued with the Presidential Decree of 29 December 2000, no. 441, actually only indicate, without solving, some fundamental questions that regard the sector, postponing their settlement, without any time limits, to subsequent second degree regulations.As regards the more strictly library themes of interest, the necessity to solve the problems of the legal deposit drove the AIB to revive the bill proposal, which had already been discussed and had arrived at the threshold of final approval in Parliament in the 13th legislature.During the year 2001, moreover, the European Parliament and the European Union Council finally approved the Directive 2001/29/CE, that aims at integrating the laws of the member countries regarding reproduction rights, rights of communication of works to the public and distribution rights, in reference to those works, on every kind of medium, including digital medium, subject to authors' rights. Art. 5 provides the faculty of member states to order exceptions and limitations to the above mentioned rights, to guarantee the right balance between authors' rights and other social interests. This article furthermore contains the "exceptions" that are to the advantage of libraries or of didactics and scientific research.Cooperation and consortiumsThe last two years have shown considerable progress in the field of cooperation activities, confirming also in Italy the current tendencies at international level. These developments generally - but with different nuances - regard various types of libraries and involve different sectors of activity, from those already established (such as cataloguing and purchases) to emerging activities, more directly linked with the diffusion of Internet (management and development of digital resources, etc.).Access to information and the development of electronic collections are surely the areas that are most involved in the new cooperation initiatives. The university sector is that which demonstrates most vitality in this area, but a certain recent enterprise of state and public libraries should be noted. The initiatives promoted by two large university computer consortiums should also be mentioned: the Cilea and Caspur.The CiBit project for digitalisation, archiving and networking, with a special research interface for Italian literature texts should be noted.In Italian universities, as in other developed countries, the idea of creating alternative models of academic electronic publishing is being increasingly encouraged: in this field mention must be made of the initiative of the University of Florence with the Firenze University Press project.On-line cataloguesThe catalogues of Italian libraries available through Internet number 420. For the year 2001 growth stabilized around 15% and mainly regarded the local body systems, the libraries of which cover municipal or provincial areas.The Italian university OPACs (On line Public Access Catalog) form approximately 40% of the total.National Library Service (SBN) and national projectsIn the last two years the SBN network has been established as the largest public network of libraries in Italy, both due to the number of libraries participating and to the considerable increase in the information in the catalogue: at the end of the year 2001 the libraries numbered approximately 1400, the size of the national collective catalogue was 5,500,000 titles (corresponding to approximately 12 million localizations, that is mentions of the presence of the works in the participating libraries). Daily hits, also as a result of the availability on Internet of the catalogue, are currently on average 160,000 on weekdays, with high points on some days of over 200,000 hits.Other cooperation projects are underway in the field of antique books and manuscripts.The Anagrafe delle biblioteche italiane (Registry of Italian libraries) data base, it too available for consultation on Internet, provides an instrument of general information on the patrimonies, services to the public and specializations of approximately 12,500 libraries.But it is "SBN on line" that has really marked a further step forward towards the improvement of the services: from a single access point, with identical modalities, users can consult catalogues of different institutions (libraries, archives, museums); they can compile a bibliography according to their own specific requirements by integrating information sources; they can also locate documents and ask for them on loan or in reproduced form.Formation, occupation and professionItaly also considers university formation as the basis for the initial preparation of librarians. In the nineties especially, the degree course in Preservation of Cultural Heritage was a source of considerable attraction among young people and in the year 2000/01 it ended up having over 23,000 students registered in the 17 universities offering the course as well as almost 3,000 registered in various related diploma courses (Operators of Cultural Heritage), for a total of 26,339 students. As a whole this is a small sector with respect to all university education (1.6% of the total of students, 2% of those enrolled, 0.6% of those graduated or having obtained diplomas), but a large group with respect to the degree or diploma "arts" group into which it is statistically inserted (16% of those registered, 23% of those enrolled and 7% of those graduated or having obtained diplomas).In the year 2000/01, the first year of the "3+2" university reform, among the 42 first level degree classes, that in Sciences of Cultural Heritage is at the 12th place as regards number of enrolled (9079) and is generally in the first place among the characteristic courses in the Arts Faculty (in the order Arts, Sciences and technologies of figurative arts, of music, entertainment and fashion, Philosophy, Historical Sciences). Sixty-six percent of the students in the degree courses in the archive-library field are female.As a whole the number of students registered is certainly greatly increased with the new courses (9079 enrolled in 2001/02 as against the 5920 of the previous year, +53%). The current offer is of 71 courses in 41 universities: among these, 9 (in a like number of universities) are specifically dedicated to the formation of librarians and archivists, while 33, 2 of which by distance-learning, have a general nature (18 with a specialization for librarians and archivists), and 29 regard other specific sectors (artistic, archaeological, musical, etc., heritage ). Overall, there are therefore at least 27 courses aimed at the formation of librarians, in 26 universities and with locations in 25 different cities.Those who graduated in Cultural Heritage have up to now obtained rapid and effective insertion into the world of work, initially above all with assistance initiatives or contract jobs but also with permanent employment, demonstrating among other things their capacity to temporarily or permanently exploit employment opportunities even in related fields (publishing, multimedia production, Web services, communications, etc.).Generally speaking, the offer of long-term employment in public administration is about 180 positions per year. The main employers are the local bodies, with 64%, followed by the Universities with 27%. Absent for years now is the Ministry for Cultural Heritage (except for two small competitions in 1998 and 1999); some offers come from the sector of research (institutions of the CNR and other bodies, for 7% in the three-year period under consideration), and exceptionally from other public bodies.From the point of view of geographic distribution, the vast majority of the jobs offered is in the North (72%, as against 11% in the Centre and 17% in the South and in the islands), and the percentage exceeds 80% for places in the local bodies: about half of the jobs offered by Italian local bodies are in the region of Lombardy; this is followed at a great distance by Emilia Romagna and then the Veneto region. In the universities, the distribution is a little less unbalanced, again with Lombardy in the first place but with a good offer also in regions of the Centre (Lazio) or of the South (Campania, Puglia).The offer of contract employment or with assistance positions is very active, both through competitions and screening for contract jobs in public administrations and through the search for assistants by service companies, mainly in the field of cataloguing, and of library structures: we can consider that through these forms of selection approximately 300 persons per year find temporary employment.The Italian Libraries Association and the Professional RegisterAn indicator of the dynamism of the profession is given also by the activity of the Italian Libraries Association (AIB) which, during the year 2000 extended to include all twenty Italian regions and considerably increased its number of members: 4407 members (+2% with respect to the previous year). This shows a much larger and clearer growth than that of employment in the sector, which therefore testifies to a greater group thrust, of "self-recognition" and identification, while a considerable number of occasional registrations remain: these are not renewed with any continuity.Since 1998, the AIB manages the Italian Professional Register of librarians, a private register that was established along the lines indicated by the European directives on the recognition of professional titles and by the bills on the unrecognised professions presented in the last legislatures but not yet approved. On 31 December 2001 the Register had 566 qualified librarians enrolled, 160 of which enrolled during the last year.The following persons co-operated to this work: Giovanni Solimine (Introduction); Luca Bellingeri, Gianni Lazzari (Law); Anna Maria Mandillo (Law, SBN and national projects); Gabriele Mazzitelli, Serafina Spinelli (Academic library systems); Tommaso Giordano (Cooperation and consortia); Antonella De Robbio (Italian OPACs); Vanni Bertini (Automation systems in Italy); Alberto Petrucciani (Training, employment and profession). ; Hanno collaborato alla redazione del Rapporto: Giovanni Solimine (Introduzione); Luca Bellingeri, Gianni Lazzari (Legislazione); Anna Maria Mandillo (Legislazione, SBN e progetti nazionali); Gabriele Mazzitelli, Serafina Spinelli (Sistemi bibliotecari di ateneo); Tommaso Giordano (Cooperazione e consorzi); Antonella De Robbio (OPAC italiani); Vanni Bertini (Sistemi di automazione in Italia); Alberto Petrucciani (Formazione, occupazione e professione).

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Open Access#8432013

Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk

Couch, Fergus J; Durán, Mercedes; Antoniou, Antonis C

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- CIMBA et al. ; BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. ; The study was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341), grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure; Cancer Research UK grants C12292/A11174 and C1287/A10118; the European Commission's Seventh Framework Programme grant agreement 223175 (HEALTH-F2-2009-223175). Breast Cancer Family Registry Studies (BCFR): supported by the National Cancer Institute, National Institutes of Health 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), Cancer Prevention Institute of California (U01 CA69417), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), and University of Melbourne (U01 CA69638). The Australian BCFR 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. Melissa C. Southey is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. Carriers at FCCC were also identified with support from National Institutes of Health grants P01 CA16094 and R01 CA22435. The New York BCFR was also supported by National Institutes of Health grants P30 CA13696 and P30 ES009089. The Utah BCFR was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH grant UL1 RR025764, and by Award Number P30 CA042014 from the National Cancer Institute. Baltic Familial Breast Ovarian Cancer Consortium (BFBOCC): BFBOCC is partly supported by Lithuania (BFBOCC-LT), Research Council of Lithuania grant LIG-19/2010, and Hereditary Cancer Association (Paveldimo vėžio asociacija). ; Latvia (BFBOCC-LV) is partly supported by LSC grant 10.0010.08 and in part by a grant from the ESF Nr.2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016.BRCA-gene mutations and breast cancer in South African women (BMBSA): BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. Beckman Research Institute of the City of Hope (BRICOH): Susan L. Neuhausen was partially supported by the Morris and Horowitz Families Endowed Professorship. BRICOH was supported by NIH R01CA74415 and NIH P30 CA033752. Copenhagen Breast Cancer Study (CBCS): The CBCS study was supported by the NEYE Foundation. Spanish National Cancer Centre (CNIO): This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrileña Foundation (FMMA) and SAF2010-20493. City of Hope Cancer Center (COH): The City of Hope Clinical Cancer Genetics Community Research Network is supported by Award Number RC4A153828 (PI: Jeffrey N. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. CONsorzio Studi ITaliani sui Tumori Ereditari Alla Mammella (CONSIT TEAM): CONSIT TEAM was funded by grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Italian Association for Cancer Research (AIRC, IG 8713), Italian Minitry of Health (Extraordinary National Cancer Program 2006, "Alleanza contro il Cancro" and "Progetto Tumori Femminili), Italian Ministry of Education, University and Research (Prin 2008) Centro di Ascolto Donne Operate al Seno (CAOS) association and by 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'). German Cancer Research Center (DKFZ): The DKFZ study was supported by the DKFZ. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON): HEBON is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the NWO grant 91109024, the Pink Ribbon grant 110005, and the BBMRI grant CP46/NWO. ; Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE): EMBRACE is supported by 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. Rosalind A. Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer Canter (FCCC): The authors acknowledge support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC): The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers (GEMO): The GEMO study was supported by the Ligue National Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award and the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program. Gynecologic Oncology Group (GOG): This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and Tissue Bank (CA 27469), Statistical and Data Center (CA 37517), and GOG's Cancer Prevention and Control Committtee (CA 101165). Drs. Mark H. Greene and Phuong L. Mai were supported by funding from the Intramural Research Program, NCI, NIH. Hospital Clinico San Carlos (HCSC): HCSC was supported by RETICC 06/0020/0021, FIS research grant 09/00859, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitivity, and the European Regional Development Fund (ERDF). ; Helsinki Breast Cancer Study (HEBCS): The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, the Nordic Cancer Union, and the Sigrid Juselius Foundation. Study of Genetic Mutations in Breast and Ovarian Cancer patients in Hong Kong and Asia (HRBCP): HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr. Ellen Li Charitable Foundation, Hong Kong. Molecular Genetic Studies of Breast and Ovarian Cancer in Hungary (HUNBOCS): HUNBOCS was supported by Hungarian Research Grant KTIA-OTKA CK-80745 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/ÖP-9. Institut Català d'Oncologia (ICO): The ICO study was supported by the Asociación Española Contra el Cáncer, Spanish Health Research Foundation, Ramón Areces Foundation, Carlos III Health Institute, Catalan Health Institute, and Autonomous Government of Catalonia and contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI09/02483, PI10/01422, PI10/00748, 2009SGR290, and 2009SGR283. International Hereditary Cancer Centre (IHCC): Supported by the Polish Foundation of Science. Katarzyna Jaworska is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. Iceland Landspitali–University Hospital (ILUH): The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INterdisciplinary HEalth Research Internal Team BReast CAncer susceptibility (INHERIT): INHERIT work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program, the Canadian Breast Cancer Research Alliance grant 019511 and the Ministry of Economic Development, Innovation and Export Trade grant PSR-SIIRI-701. Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. ; Istituto Oncologico Veneto (IOVHBOCS): The IOVHBOCS study was supported by Ministero dell'Istruzione, dell'Università e della Ricerca and Ministero della Salute ("Progetto Tumori Femminili" and RFPS 2006-5-341353,ACC2/R6.9"). Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab): kConFab is supported by grants from the National Breast Cancer Foundation and 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. Amanda B. Spurdle is an NHMRC Senior Research Fellow. The Clinical Follow Up Study was funded from 2001–2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333. Mayo Clinic (MAYO): MAYO is 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. McGill University (MCGILL): The McGill Study was supported by Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation, and Export Trade. Memorial Sloan-Kettering Cancer Center (MSKCC): The MSKCC study was supported by Breast Cancer Research Foundation, Niehaus Clinical Cancer Genetics Initiative, Andrew Sabin Family Foundation, and Lymphoma Foundation. Modifier Study of Quantitative Effects on Disease (MODSQUAD): MODSQUAD was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). Women's College Research Institute, Toronto (NAROD): NAROD was supported by NIH grant: 1R01 CA149429-01. National Cancer Institute (NCI): Drs. Mark H. Greene and Phuong L. Mai were supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD. National Israeli Cancer Control Center (NICCC): NICCC is supported by Clalit Health Services in Israel. Some of its activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. N. N. Petrov Institute of Oncology (NNPIO): The NNPIO study has been supported by the Russian Foundation for Basic Research (grants 11-04-00227, 12-04-00928, and 12-04-01490), the Federal Agency for Science and Innovations, Russia (contract 02.740.11.0780), and through a Royal Society International Joint grant (JP090615). The Ohio State University Comprehensive Cancer Center (OSU-CCG): OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. ; South East Asian Breast Cancer Association Study (SEABASS): SEABASS is supported by the Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. Sheba Medical Centre (SMC): The SMC study was partially funded through a grant by the Israel Cancer Association and the funding for the Israeli Inherited Breast Cancer Consortium. Swedish Breast Cancer Study (SWE-BRCA): SWE-BRCA collaborators are supported by the Swedish Cancer Society. The University of Chicago Center for Clinical Cancer Genetics and Global Health (UCHICAGO): UCHICAGO is supported by grants from the US National Cancer Institute (NIH/NCI) 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. University of California Los Angeles (UCLA): The UCLA study was supported by the Jonsson Comprehensive Cancer Center Foundation and the Breast Cancer Research Foundation. University of California San Francisco (UCSF): The UCSF study was supported by the UCSF Cancer Risk Program and the Helen Diller Family Comprehensive Cancer Center. United Kingdom Familial Ovarian Cancer Registries (UKFOCR): UKFOCR was supported by a project grant from CRUK to Paul Pharoah. University of Pennsylvania (UPENN): The UPENN study was supported by the National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855), Breast Cancer Research Foundation, Rooney Family Foundation, Susan G. Komen Foundation for the Cure, and the Macdonald Family Foundation. Victorian Familial Cancer Trials Group (VFCTG): The VFCTG study was supported by the Victorian Cancer Agency, Cancer Australia, and National Breast Cancer Foundation. Women's Cancer Research Initiative (WCRI): The WCRI at the Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN). ; Peer Reviewed

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Open Access#8442012

Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs

Bousquet, J; Schuenemann, H. J; Samolinski, B; Demoly, P; Baena-Cagnani, Carlos E; Bachert, C; Bonini, S; Boulet, L. P

Bousquet, J; Schuenemann, H. J; Samolinski, B; Demoly, P; Baena-Cagnani, Carlos E; Bachert, C; Bonini, S; Boulet, L. P; Bousquet, P. J; Brozek, J. L; Canonica, G. W; Casale, T. B; Cruz, A. A; Fokkens, W. J; Fonseca, J. A; van Wijk, R. Gerth; Grouse, L; Haahtela, T; Khaltaev, N; Kuna, P; Lockey, R. F; Carlsen, K. C. Lodrup; Mullol, J; Naclerio, R; O'Hehir, R. E; Ohta, K; Palkonen, S; Papadopoulos, N. G; Passalacqua, G; Pawankar, R; Price, D; Ryan, D; Simons, F. E. R; Togias, A; Williams, D; Yorgancioglu, A; Yusuf, O. M; Aberer, W; Adachi, M; Agache, I; Ait-Khaled, N; Akdis, C. A; Andrianarisoa, A; Annesi-Maesano, I; Ansotegui, I. J; Baiardini, I; Bateman, E. D; Bedbrook, A; Beghe, B; Beji, M; Bel, E. H; Ben Kheder, A; Bennoor, K. S; Bergmann, K. C; Berrissoul, F; Bieber, T; Jensen, C. Bindslev; Blaiss, M. S; Boner, A. L; Bouchard, J; Braido, F; Brightling, C. E; Bush, A; Caballero, F; Calderon, M. A; Calvo, M. A; Camargos, P. A. M; Caraballo, L. R; Carlsen, K. H; Carr, W; Cepeda, A. M; Cesario, A; Chavannes, N. H; Chen, Y. Z; Chiriac, A. M; Chivato Perez, T; Chkhartishvili, E; Ciprandi, G; Costa, D. J; Cox, L; Custovic, A; Dahl, R; Darsow, U; De Blay, F; Deleanu, D; Denburg, J. A; Devillier, P; Didi, T; Dokic, D; Dolen, W. K; Douagui, H; Dubakiene, R; Durham, S. R; Dykewicz, M. S; El-Gamal, Y; El-Meziane, A; Emuzyte, R; Fiocchi, A; Fletcher, M; Fukuda, T; Gamkrelidze, A; Gereda, J. E; Gonzalez Diaz, S; Gotua, M; Guzman, M. A; Hellings, P. W; Hellquist-Dahl, B; Horak, F; Hourihane, J. O'B; Howarth, P; Humbert, M; Ivancevich, J. C; Jackson, C; Just, J; Kalayci, O; Kaliner, M. A; Kalyoncu, A. F; Keil, T; Keith, P. K; Khayat, G; Kim, Y. Y; N'Goran, B. Koffi; Koppelman, G. H; Kowalski, M. L; Kull, I; Kvedariene, V; Larenas-Linnemann, D; Le, L. T; Lemiere, C; Li, J; Lieberman, P; Lipworth, B; Mahboub, B; Makela, M. J; Martin, F; Marshall, G. D; Martinez, F. D; Masjedi, M. R; Maurer, M; Mavale-Manuel, S; Mazon, A; Melen, E; Meltzer, E. O; Mendez, N. H; Merk, H; Mihaltan, F; Mohammad, Y; Morais-Almeida, M; Muraro, A; Nafti, S; Namazova-Baranova, L; Nekam, K; Neou, A; Niggemann, B; Nizankowska-Mogilnicka, E; Nyembue, T. D; Okamoto, Y; Okubo, K; Orru, M. P; Ouedraogo, S; Ozdemir, C; Panzner, P; Pali-Schoell, I; Park, H. S; Pigearias, B; Pohl, W; Popov, T. A; Postma, D. S; Potter, P; Rabe, K. F; Ratomaharo, J; Reitamo, S; Ring, J; Roberts, R; Rogala, B; Romano, A; Rodriguez, M. Roman; Rosado-Pinto, J; Rosenwasser, L; Rottem, M; Sanchez-Borges, M; Scadding, G. K; Schmid-Grendelmeier, P; Sheikh, A; Sisul, J. C; Sole, D; Sooronbaev, T; Spicak, V; Spranger, O; Stein, R. T; Stoloff, S. W; Sunyer, J; Szczeklik, A; Todo-Bom, A; Toskala, E; Tremblay, Y; Valenta, R; Valero, A. L; Valeyre, D; Valiulis, A; Valovirta, E; Van Cauwenberge, P; Vandenplas, O; van weel, C; Vichyanond, P; Viegi, G; Wang, D. Y; Wickman, M; Woehrl, S; Wright, J; Yawn, B. P; Yiallouros, P. K; Zar, H. J; Zernotti, M. E; Zhong, N; Zidarn, M; Zuberbier, T; World Hlth Org Collaborating Ctr

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified ARas mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. in its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIAWorld Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children. (J Allergy Clin Immunol 2012;130:1049-62.) ; Stallergenes ; ALK-Abello ; European Academy of Allergy and Clinical Immunology (EAACI) ; MSD ; Novartis ; Nycomed/Takeda ; PHADIA/Thermo Fischer ; 3M ; AstraZeneca ; GlaxoSmithKline ; Merck Frosst ; Altair ; Amgen ; Asmacure ; Boehringer-Ingelheim ; Genentech ; Pharmaxis ; Schering ; Wyeth ; Ache ; Brazilian Research Council ; Fundacao de Amparo a Pesquisa da Bahia ; Fundacao Ciencia e Tecnologia ; Sociedade Portuguesa de Alergologia e Immunologia Clinica ; Abdi Ibrahim ; OrionPharma ; Nasonebs ; Merck ; McNeal ; Chiesi ; Nycomed ; Air Liquid Healthcare ; Mundipharma ; Almirall ; Kyorin ; Teva ; UK National Health Service ; Aerocrine ; AKL Ltd ; PREDICTA ; Swiss National Science Foundation ; MeDALL ; Global Allergy and Asthma European Network (GA 2LEN) ; Christine Kuthe Center for Allergy Research and Education ; Faes Farma ; Bial ; Johnson Johnson ; Sanofi ; HAD treasurer ; Innovative Medicine Initiative (EU) ; Helse Sor-Ost RHF (Southern and Eastern Norway Regional Health Authority) ; MEDA ; Alcon ; ISTA ; Thermo-Fisher ; Airsonett ; Medical Research Council ; Moulton Charitable Trust ; AB Science ; Canadian Institutes for Health Research ; AllerGen NCE ; Merck/Schering-Plough ; Circassia ; University Hospital ; Medical School of Universidad Autonoma de Nuevo Leon, Mexico ; Children's Research Foundation (Ireland) ; Danone ; Food Standards Agency (United Kingdom) ; European Union (EU) ; DTG ; Netherlands Asthma Foundation ; Merck-Sharp-Dohme, Mexico ; Allerquim Mexico ; Abbott ; Apotex ; HRA ; MedImmune ; Schering-Plough ; Proctor Gamble ; Sunovion (Sepracor) ; Phadia ; Servier ; CSC JohnsonJohnson ; Oxygen Plus ; New Medics ; European Respiratory Society ; Societe de Pneumologie de Langue Francaise Asthma ; Ministry of Health, Welfare, and Labor ; Altana ; Takeda ; UCB ; Uriach advisory board ; NAPP ; Royal College of GPs Clinical Champion in Allergy ; Agency for Healthcare Research and Quality (AHRQ) ; AnseII ; Bayer Schering ; OST ; Fujisawa ; IHAL ; Henkel ; Kryolan ; Leti ; MSO ; Procter and Gamble ; Sanofi-Aventis ; Scientific Advisory Board for the German Society for Allergy and Clinical Immunology ; German Federal Ministry of Consumer Protection ; European Centre for Allergy Research Foundation (ECARF) ; Hop Arnaud Villeneuve, Dept Resp Dis, Univ Hosp, Montpellier, France ; INSERM, U1018, CESP Ctr Res Epidemiol & Populat Hlth, Resp & Environm Epidemiol Team, Villejuif, France ; McMaster Univ, Dept Clin Epidemiol & Biostat & Med, Hamilton, ON, Canada ; Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland ; Univ Hosp Montpellier, Hop Arnaud Villeneuve, INSERM, U657, Montpellier, France ; Catholic Univ, Fac Med, Res Ctr Resp Med CIMER, Cordoba, Argentina ; Univ Genoa, Sch Specializat, Genoa, Italy ; Univ Ghent, Dept Otorhinolaryngol, Upper Airways Res Lab, B-9000 Ghent, Belgium ; CNR, Inst Translat Pharmacol, Rome, Italy ; Univ Naples 2, Naples, Italy ; Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada ; Univ Genoa, Dept Internal Med, DIMI, I-16126 Genoa, Italy ; Creighton Univ, Dept Med, Div Allergy & Immunol, Omaha, NE 68178 USA ; Univ Fed Bahia, ProAR Nucleo Excelencia Asma, Salvador, BA, Brazil ; CNPq, Salvador, BA, Brazil ; Univ Amsterdam, Dept Otorhinolaryngol, NL-1012 WX Amsterdam, Netherlands ; Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, NL-1105 AZ Amsterdam, Netherlands ; Univ Porto, Sch Med, Dept Hlth Informat & Decis Sci, P-4100 Oporto, Portugal ; Univ Porto, Sch Med, CINTESIS, P-4100 Oporto, Portugal ; Hosp S Joao & Inst, Dept Allergy, Oporto, Portugal ; Hosp CUF Porto, Oporto, Portugal ; Erasmus MC, Dept Internal Med, Sect Allergol, Rotterdam, Netherlands ; Univ Washington, Sch Med, Seattle, WA USA ; Helsinki Univ Hosp, Dept Allergy, Skin & Allergy Hosp, Helsinki, Finland ; GARD ARIA Coordinator, Geneva, Switzerland ; Med Univ Lodz, Dept Internal Med Asthma & Allergy, Barlicki Univ Hosp, Lodz, Poland ; Univ S Florida, Coll Med, Dept Internal Med, Div Allergy & Immunol, Tampa, FL 33612 USA ; James A Haley Vet Hosp, Tampa, FL USA ; Univ Oslo, Oslo Univ Hosp, Dept Paediat, Oslo, Norway ; CIBERES, IDIBAPS, Hosp Clin, Rhinol Unit,ENT Dept, Barcelona, Spain ; CIBERES, IDIBAPS, Hosp Clin, Smell Clin,ENT Dept, Barcelona, Spain ; Univ Chicago, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA ; Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia ; Monash Univ, Melbourne, Vic 3004, Australia ; Teikyo Univ, Sch Med, Dept Med, Div Resp Med & Allergol, Tokyo 173, Japan ; EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium ; Univ Athens, Dept Allergy, Pediat Clin 2, Athens, Greece ; Nippon Med Sch, Bunkyo Ku, Tokyo 113, Japan ; Univ Aberdeen, Dept Primary Care Resp Med, Aberdeen, Scotland ; Woodbrook Med Ctr, Loughborough, Leics, England ; Univ Edinburgh, Edinburgh, Midlothian, Scotland ; Univ Manitoba, Fac Med, Winnipeg, MB, Canada ; NIAID, Bethesda, MD 20892 USA ; Univ N Carolina, Sch Pharm, Chapel Hill, NC USA ; Celal Bayar Univ, Sch Med, Dept Pulmonol, Manisa, Turkey ; Allergy & Asthma Inst, Islamabad, Pakistan ; Med Univ Graz, Dept Dermatol, Graz, Austria ; Showa Univ, Sch Med, Div Allergol & Resp Med, Tokyo 142, Japan ; Transylvania Univ, Fac Med, Brasov, Romania ; Int Union TB & Lung Dis Union, Paris, France ; Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland ; Minist Hlth, Publ Hosp Med Serv, Antananarivo, Madagascar ; INSERM, EPAR U707, Paris, France ; Univ Paris 06, EPAR, UMR S, Paris, France ; Hosp Quiron Bizkaia, Dept Allergy & Immunol, Erandio Bilbao, Spain ; Univ Cape Town, Dept Med, Fac Hlth Sci, Div Pulmonol, ZA-7925 Cape Town, South Africa ; WHO, Collaborating Ctr Asthma & Rhinitis, Montpellier, France ; Univ Modena & Reggio Emilia, Dept Oncol Hematol & Resp Dis, Modena, Italy ; Ctr Hosp Univ Rabta, Serv Pneumol Allergol, Tunis, Tunisia ; Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1105 AZ Amsterdam, Netherlands ; Hop Mami, Ariana, Tunisia ; Bangladesh Lung Fdn, Dhaka, Bangladesh ; Natl Inst Dis Chest & Hosp, Dhaka, Bangladesh ; Charite, Dept Dermatol, Allergy Ctr Charite, D-13353 Berlin, Germany ; Univ Med Ctr, Dept Dermatol & Allergy, Bonn, Germany ; Odense Univ Hosp, Dept Dermatol, DK-5000 Odense, Denmark ; Odense Univ Hosp, Allergy Ctr, DK-5000 Odense, Denmark ; Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA ; Univ Verona, Dept Paediat, I-37100 Verona, Italy ; Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada ; Hop Malbaie, La Malbaie, PQ, Canada ; Univ Leicester, Inst Lung Hlth, Leicester LE1 7RH, Leics, England ; Royal Brompton Hosp, Dept Paediat Resp Med, London SW3 6LY, England ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Sect Allergy & Clin Immunol, London, England ; Ctr Med Docente La Trinidad Caracas, Dept Immunol, Caracas, Venezuela ; Univ Austral Chile, Fac Med, Dept Pediat, Valdivia, Chile ; Univ Fed Sao Joao del Rei, Hlth Sci Ctr, Hlth Sci Postgrad Program, Divinopolis, Brazil ; Univ Cartagena, Immunol Res Inst, Cartagena de Indias, Colombia ; So Calif Res, Mission Viejo, CA USA ; Metropolitan Univ Barranquilla, Allergy & Immunol Lab, Barranquilla, Colombia ; 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Egyptian Soc Pediat Allergy & Immunol, Cairo, Egypt ; Soc Marocaine Malad Resp, Casablanca, Morocco ; Ctr Resp Dis & Allergy, Casablanca, Morocco ; Vilnius Univ, Fac Med, Vilnius, Lithuania ; Univ Milan, Sch Med, Melloni Hosp, Milan, Italy ; Educ Hlth, Warwick, England ; Dokkyo Med Univ, Mibu, Tochigi, Japan ; WHO, Country Off Georgia, Tbilisi, Rep of Georgia ; Clin Ricardo Palma, Lima, Peru ; Univ Nuevo Leon UANL, Hosp Univ, Fac Med, Monterrey, Mexico ; Ctr Allergy & Immunol, Tbilisi, Rep of Georgia ; Clin Hosp Univ Chile, Dept Med, Immunol & Allergol Div, Santiago, Chile ; Univ Hosp Leuven, Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium ; Cent Reg Denmark, Ctr Publ Hlth & Qual Improvement, Aarhus, Denmark ; Allergy Ctr Vienna W, Vienna, Austria ; Natl Univ Ireland Univ Coll Cork, Dept Paediat & Child Hlth, Cork, Ireland ; Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England ; Univ Paris 11, Serv Pneumol, Hop Antoine Beclere, AP HP,INSERM,U999, Clamart, France ; Salvador Univ, Sch Med, Dept Immunol, Buenos Aires, DF, Argentina ; Univ St Andrews, St Andrews, Fife, Scotland ; Univ Paris, APHP, Ctr Asthme & Allergies, Grp Hosp Trousseau La Roche Guyon, F-75252 Paris, France ; Hacettepe Univ, Sch Med, Pediat Allergy & Asthma Unit, Ankara, Turkey ; George Washington Univ, Sch Med, Washington, DC USA ; Inst Asthma & Allergy, Chevy Chase, MD USA ; Hacettepe Univ Hosp, Dept Chest Dis, Adult Allergy Unit, Ankara, Turkey ; Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany ; McMaster Univ, Hamilton, ON, Canada ; Hotel Dieu France, Serv Pneumol & Reanimat Med, Beirut, Lebanon ; Univ St Joseph, Fac Med, Beirut, Lebanon ; Natl Med Ctr, Seoul, South Korea ; Seoul Natl Univ, Seoul, South Korea ; Korea Asthma Allergy Fdn, Seoul, South Korea ; Ctr Hosp Univ, Serv Malad Resp, Abidjan, Cote Ivoire ; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Beatrix Childrens Hosp,Dept Pediat Pulmonol & Ped, Groningen, Netherlands ; Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland ; Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden ; Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden ; Vilnius Univ, Ctr Pulmonol & Allergol, Vilnius, Lithuania ; Vilnius Univ Hosp Santariskiu Klinikos, Vilnius, Lithuania ; Hosp Med Sur, Dept Allergy, Mexico City, DF, Mexico ; Univ Med & Pharm, Thanh Pho Ho Chi Minh, Vietnam ; Hop Sacre Coeur Montreal, Montreal, PQ, Canada ; Univ Montreal, Montreal, PQ, Canada ; Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China ; Univ Tennessee, Coll Med, Memphis, TN USA ; Univ Dundee, Ninewells Hosp, Asthma & Allergy Res Grp, Dundee, Scotland ; Dubai Hlth Author, Sharjah, U Arab Emirates ; Univ Sharjah, Sharjah, U Arab Emirates ; Univ Mississippi, Med Ctr, Div Clin Immunol & Allergy, Jackson, MS 39216 USA ; Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ USA ; Univ Arizona, Inst BIO5, Tucson, AZ USA ; Shahid Beheshti Univ Med Sci, NRITLD, Tehran, Iran ; Shahid Beheshti Univ Med Sci, Chron Resp Dis Res Ctr, Tehran, Iran ; Charite, Dept Dermatol & Allergy, D-13353 Berlin, Germany ; Maputo Cent Hosp, Dept Peadiat, Maputo, Mozambique ; Eduardo Mondlane Univ, Fac Med, Maputo, Mozambique ; Childrens Hosp La Fe, Unit Pediat Allergy & Pneumol, Valencia, Spain ; Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden ; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden ; Univ Calif San Diego, Allergy & Asthma Med Grp, San Diego, CA 92103 USA ; Univ Calif San Diego, Res Ctr, San Diego, CA 92103 USA ; IMSS, Dept Allergy & Clin Immunol, Ctr Med Nacl Siglo 21, Mexico City, DF, Mexico ; Univ Aachen, Dept Dermatol, Aachen, Germany ; Inst Pneumol Marius Nasta, Bucharest, Romania ; Tishreen Univ, Sch Med, Dept Internal Med, WHO EMRO Collaborating Ctr Training & Res Chron R, Latakia, Syria ; CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal ; Univ Padua, Dept Pediat, Food Allergy Referral Ctr Veneto Reg, Padua, Italy ; Mustapha Hosp, Algiers, Algeria ; Sci Ctr Childrens Hlth RAMS, Moscow, Russia ; Hosp Hospitaller Bros Buda, Budapest, Hungary ; Charite, Allergie Ctr Charite ECARF, Dept Dermatol Venerol & Allergy, D-13353 Berlin, Germany ; German Red Cross Hosp Westend, Berlin, Germany ; Jagiellonian Univ, Sch Med, Dept Pulmonol, Krakow, Poland ; Kinshasa Univ, ENT Dept, Kinshasa, Zaire ; Chiba Univ Hosp, Dept Otorhinolaryngol, Chiba, Japan ; Nippon Med Sch, Dept Otolaryngol, Bunkyo Ku, Tokyo 113, Japan ; Ctr Hosp Univ Pediat Charles de Gaulle, Ouagadougou, Burkina Faso ; Marmara Univ, Div Pediat Allergy & Immunol, Istanbul, Turkey ; Mem Hlth Grp, Istanbul, Turkey ; Charles Univ Prague, Fac Med Plzen, Dept Immunol & Allergol, Prague, Czech Republic ; MESSERLI Res Inst, Vienna, Austria ; Med Univ Vienna, Univ Vet Med Vienna, Vienna, Austria ; Univ Vienna, Vienna, Austria ; Ajou Univ, Sch Med, Suwon 441749, South Korea ; NICE, Paris, France ; Soc Pneumol Langue Francaise, Paris, France ; Krankenhaus Hietzing, Karl Landsteiner Inst Expt & Clin Pneumol, Dept Pulm Med, Vienna, Austria ; Alexanders Univ Hosp, Clin Allergy & Asthma, Sofia, Bulgaria ; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Dept Pulmonol, Groningen, Netherlands ; Univ Cape Town, Lung Inst, ZA-7925 Cape Town, South Africa ; Groote Schuur Hosp, ZA-7925 Cape Town, South Africa ; Leiden Univ, Dept Pulmonol, Med Ctr, Leiden, Netherlands ; Grosshansdorf Clin, Grosshansdorf, Germany ; Hop Prive Athis Mons, Serv Pneumol, Athis Mons, France ; Helsinki Univ Hosp, Dept Dermatol, Skin & Allergy Hosp, Helsinki, Finland ; Tech Univ Munich, CKCARE, Dept Dermatol Allergy Biederstein, Munich, Germany ; Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA ; Med Univ Silesia, Dept & Clin Internal Dis Allergol & Clin Immunol, Katowice, Poland ; Complesso Integrato Columbus, Allergy Unit, Rome, Italy ; IRCCS Oasi Maria SS, Troina, Italy ; Son Pisa Primary Care Ctr, IB Salut Balear Hlth Serv, Int Primary Care Resp Grp, Palma de Mallorca, Spain ; Hosp Luz, Immunoallergy Dept, Lisbon, Portugal ; Univ Missouri, Kansas City Sch Med, Kansas City, MO 64110 USA ; Childrens Mercy Hosp, Kansas City, MO USA ; Emek Med Ctr, Afula, Israel ; Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel ; Ctr Med Docente La Trinidad, Dept Allergy & Clin Immunol, Caracas, Venezuela ; UCL, Royal Natl TNE Hosp, London, England ; Univ Zurich Hosp, Dept Dermatol, Allergy Unit, CH-8091 Zurich, Switzerland ; Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland ; Universidade Federal de São Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, São Paulo, Brazil ; Natl Ctr Cardiol & Internal Med, Bishkek, Kyrgyzstan ; Ctr ACI Immunoflow, Czech Initiat Asthma, Prague, Czech Republic ; GAAPP, Vienna, Austria ; Ctr Res Environm Epidemiol CREAL, Barcelona, Spain ; Pontificia Univ Catolica RGS, Sch Med, Porto Alegre, RS, Brazil ; Univ Nevada, Sch Med, Reno, NV 89557 USA ; Hosp Mar, Municipal Inst Med Res IMIM, Barcelona, Spain ; CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain ; Univ Pompeu Fabra UPF, Barcelona, Spain ; Jagiellonian Univ, Coll Med, Krakow, Poland ; Coimbra Univ Hosp, Immunoallergy Dept, Coimbra, Portugal ; Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA ; Finnish Inst Occupat Hlth, Helsinki, Finland ; Univ Laval, Fac Med, Dept Obstet & Gynecol, Laval, PQ, Canada ; Med Univ Vienna, Christian Doppler Lab Allergy Res, Div Immunopathol, Dept Pathophysiol & Allergy Res,Ctr Pathophysiol, Vienna, Austria ; Hosp Clin Barcelona, Dept Pneumol, Allergy Unit, Immunoallergia Resp Clin, Barcelona, Spain ; IDIBAPS, Barcelona, Spain ; CIBERES, Barcelona, Spain ; Univ Paris 13, Bobigny, France ; Avicenne Hosp, AP HP, Bobigny, France ; Vilnius Univ, Fac Med, Dept Paediat, Vilnius, Lithuania ; Lithuanian Natl Council Childs Hlth, Vilnius, Lithuania ; Terveystalo Turku, Allergy Clin, Turku, Finland ; Univ Turku, Dept Lung Dis & Clin Immunol, Turku, Finland ; Univ Ghent, Dept Otorhinolaryngol, B-9000 Ghent, Belgium ; Catholic Univ Louvain, Univ Hosp Mt Godinne, Yvoir, Belgium ; Radboud Univ Nijmegen, Med Ctr, Dept Primary & Community Care, NL-6525 ED Nijmegen, Netherlands ; Siriraj Hosp, Fac Med, Dept Pediat, Bangkok, Thailand ; CNR, IBIM, Palermo, Italy ; Clin Physiol IFC, Pisa, Italy ; Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore ; Floridsdorf Allergy Ctr FAZ, Vienna, Austria ; Med Univ Vienna, Dept Dermatol, DIAID, Vienna, Austria ; Bradford Teaching Hosp Fdn Trust, Bradford Inst Hlth Res, Bradford, W Yorkshire, England ; Olmsted Med Ctr, Dept Res, Rochester, MN USA ; Univ Minnesota, Dept Family & Community Hlth, Rochester, MN USA ; Harvard Univ, Sch Publ Hlth, Cyprus Int Inst Environm & Publ Hlth Assoc, Limassol, Cyprus ; Cyprus Univ Technol, Limassol, Cyprus ; Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, ZA-7925 Cape Town, South Africa ; Catholic Univ Cordoba, Sch Med, Dept Otorhinolaryngol, Cordoba, Argentina ; Guangzhou Med Univ, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China ; Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China ; Univ Clin Resp & Allerg Dis, Golnik, Slovenia ; Charite, Network Excellence, Global Allergy & Asthma European Network GA2LEN, D-13353 Berlin, Germany ; Universidade Federal de São Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, São Paulo, Brazil ; Web of Science

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Le industrie goriziane e l'istituto per la promozione delle industrie di Gorizia1903-1914

Inoue, Naoko

2006/2007 ; Questa tesi mette in rilievo, con particolare attenzione, l'attività dell' "Istituto per il Promovimento delle Industrie in Gorizia" sotto l'Impero Austro-Ungarico, dal 1902 al 1914. Lo scopo della ricerca è chiarire le caratteristiche della società multiculturale goriziana in un periodo di gravi sconvolgimenti nazionali per quanto riguarda l'attività economica promossa e protetta dall'Impero. Nella tesi si osserva attentamente la funzione dell' Istituto che nacque nel 1902, su iniziativa della Camera di Commercio e d'Industria di Gorizia, al fine di sostenere le piccole imprese locali promovendo, secondo la legge austriaca del 9 aprile 1873, la costituzione di cooperative di consumo e consorzi per l'acquisto di materie prime, di produzione e vendita. Fu un ente sociale autonomo, retto con sussidi finanziari del Ministero del commercio, della Dieta provinciale in cui esisteva una maggioranza italiana, della Camera di Commercio e dei Comuni della provincia. Tale ente godette, inoltre, di alcuni finanziamenti da istituti di credito locali. Amministrato da un Curatorio (das Kuratorium des Gewerbefoerderungsinstitutes Geweerbeförderungsdienst des k.k. Handels) costituitosi nel 1903, cui partecipavano tutti gli enti sostenitori mediante propri delegati; presieduto inizialmente da Ernesto Holzer, poi da Roberto Penso, l'Istituto si sviluppò fino a comprendere diversi uffici e servizi: ufficio della mediazione del lavoro, la biblioteca aperta alla consultazione pubblica, la Scuola speciale di perfezionamento per pittori decoratori ed arti affini, oltre ad una serie diversificata di corsi di formazione professionale in tutta la provincia. Tra le iniziative va annoverata quella di promozione degli artigianati domestici, già esistenti, tra cui quella del ricamo del merletto. Vennero, inoltre, organizzate numerose esposizioni e mostre delle opere dei frequentatori dei corsi professionali. Il materiale raccolto è composto da libri scientifici pubblicati e da documenti conservati in archivi pubblici. Questi ultimi si trovano classificati principalmente nell'inventario E.N.A.P.I. (l'Ente Nazionale per l'Artigianato e le Piccole Industrie), numerosi nell'Archivio di Stato di Gorizia. Non esiste nessuna pubblicazione che esamina complessivamente le serie dei documenti E.N.A.P.I. e, pertanto, il candidato ha svolto la ricerca con particolare attenzione a questi documenti cartacei degli archivi. Le carte, ben conservate, si presentano scritte in lingua italiana, slovena e tedesca. E' stata seguita la traccia del sommario originale, mantenendo l'ordinamento creato dall'Ente. Nella parte integrativa, versata in un secondo momento rispetto alla prima, si è cercato di ricreare un sommario virtuale, ricalcando l'ordinamento iniziale; è piuttosto evidente dalla tipologia delle carte, che negli anni '60 fosse stato creato un nuovo sommario dall'Ente stesso, ma non è stato possibile reperirlo. Dopo gli archivi aggregati, l'inventario continua con le carte dell'Istituto Nazionale Fascista, (INFAPLI), sorto nel 1938, e il cui materiale è giunto incompleto. Per cogliere i valori ed i significati della storia dell'istruzione professionale e la fondazione e le attività dell'Istituto per il Promovimento delle Industrie in Gorizia, è indispensabile capire bene la situazione socio-economica della Contea tra il 1850 ed il 1914. Nel Capitolo 1, quindi, si esplica l'economia austriaca tra il 1850 ed il 1873 e la fondazione delle Camere di Commercio e d'Industria sotto l'Austria, comprende anche la fondazione della Camera goriziana. I rivolgimenti rivoluzionari del 1848-1849 rappresentano, per l'Austria, la presa di coscienza della debolezza politica, interna ed internazionale, della monarchia. La scarsa rappresentatività del ceto imprenditoriale austriaco dipende da un complesso di fattori, storici e sociali, che ne frenano l'ascesa, riducono il suo impatto sul corpo sociale, e limitano in generale le possibilità di modernizzare l'apparato produttivo dello stato. Le Camere di Commercio e Industria nascono in Austria nel 1850, quindi, con un peso politico molto scarso, e il loro ruolo più importante risiede nella tempestiva acquisizione e nella trasmissione di informazioni sull'evoluzione della struttura produttiva dell'Impero. Tra il 1857 ed il 1859 si verifica un rallentamento del ciclo economico a livello internazionale e tale rallentamento tocca anche l'Austria, e la crisi economica culmina nel 1859, uno degli anni peggiori per la dinastia. Per rimettere in movimento la macchina degli investimenti lo stato stesso propone un nuovo piano di costruzione ferroviarie in grado di sanare gli handicap infrastrutturali del paese. La disastrosa guerra del 1866, tuttavia, impedisce ancora una volta il recupero dell'economia imperiale. Una ripresa di una certa durata si verifica solo dopo l'accordo con l'Ungheria nel 1867 e la nascita della duplice monarchia. La raggiunta stabilità interna assicura anche il decollo dell'economia. Gli anni tra il 1867 ed il 1873 sono conosciuti come l'Epoca degli Affari. Gli investimenti azionari subiscono forti rialzi, ma ancora una volta si tratta di una bolla speculativa, che termina con il clamoroso crac del 1873. La falcidia di imprese provocata dal crollo del 1873 non è, in ogni modo, solo un fatto negativo. La crisi favorisce l'eliminazione di molte aziende tradizionali e pone le basi di una modernizzazione industriale, i cui effetti si vedranno, però, solo alla fine del secolo. Nel 1850, anche a Gorizia, è istituita la Camera di Commercio presieduta da Ettore Ritter a cui va attribuita la paternità della "grande industria" di Gorizia. Una delle prime iniziative della Camera è l'organizzazione di una vetrina delle attività produttive goriziane. Infatti, nei quattro rapporti che furono pubblicati nella seconda metà del XIX secolo, vengono trattati tutti gli aspetti connessi al Circolo, come vedremo nei prossimi capitoli. Nel Capitolo 2 esaminiamo le vicende dell'economia provinciale tra il 1850 ed il 1880, principalmente con i primi due rapporti camerali di Gorizia: il Rapporto generale della Camera di Commercio ed Industria del Circolo di Gorizia rassegnato all'i. r. Ministero del Commercio sulle notizie statistiche desunte a tutto il 1858 edito nel 1859 ed il Rapporto della Camera di Commercio e Industria di Gorizia rassegnato all'i. r. Ministero del Commercio sopra le notizie statistiche degli anni 1870-1871-1872 edito nel 1873. Secondo il primo rapporto pubblicato, il Circolo goriziano fu caratterizzato da un'economia prevalentemente agricola attorno alla metà del secolo, nel cui ambito la produzione di seta greggia rappresenta un'importante risorsa. Si pose già il problema di conservare un assetto territoriale equilibrato per non danneggiare le risorse fondiarie ed evitare lo spopolamento della montagna e delle campagne, fonte di danni per l'intera comunità provinciale. La componente industriale del Circolo goriziano è, pertanto, basata sulla produzione di tessuti o di filati. Essa comprende ditte che operano con metodi dai più arcaici fino alla produzione di fabbrica. In questo senso il Rapporto ci fornisce una preziosa istantanea di un mondo in trasformazione in cui caratteri antichi convivono con tecniche moderne. Tale è una caratteristica propria di tutto l'Ottocento europeo che non deve essere considerato il secolo della rivoluzione industriale tout court. Esso è un periodo di transizione per l'Europa continentale, caratterizzato da contraddizioni interne e ritardi relativi tra i vari paesi, in relazione sia alla loro collocazione geografica sia alle componenti sociali dominanti. Nella seconda relazione, rispetto alla precedente, si nota un ampliamento delle tabelle e delle notizie statistiche, mentre l'inserimento di brevi monografie è limitato allo sviluppo dell'associazionismo e alla descrizione dell'esperienza delle industrie Ritter, in relazione alla colonia operaia di Straccis. L'avvenimento più importante nel periodo che tratta il Rapporto è l'arrivo della ferrovia a Gorizia, nel 1860, che rappresenta il superamento del relativo isolamento del capoluogo in fatto di comunicazioni e la possibilità di collegarsi ai grandi processi economici europei. Grazie alla Ferrovia Meridionale affluiscono, infatti, molti viaggianti, e il capoluogo della Contea è reso prospero per "un'affluenza straordinaria dei forestieri che fuggendo le nebbie ed i freddi nordici decantano la mitezza del suo clima e le delizie dei suoi dintorni". La perdita del Veneto nel 1866 favorì i produttori agricoli della Contea a, quasi, monopolizzare il mercato di Trieste. Sfortunatamente, nonostante tutte le favorevoli condizioni di cui si è parlato, il messaggio cade nel momento di una profonda crisi finanziaria, che segna la fine della Gründer Zeit e l'inizio di una lunga depressione. Dopo il 1873 occorre quindi un rallentamento dello sviluppo economico generale nella Contea, legato agli insufficienti investimenti individuali e sociali. Nel Capitolo 3: valutiamo le vicende dell'economia provinciale tra il 1880 ed il 1914 principalmente con le relazioni camerali divulgate nel 1889 e nel 1898: la Relazione sommaria della Camera di Commercio ed Industria di Gorizia rassegnata all'i. r. Ministero del Commercio intorno alle condizioni del suo distretto nell'anno 1888 ed il Rapporto statistico sulle condizioni dell'economia nazionale per il quinquennio 1891-1895 nel distretto della Camera di Commercio ed Industriadi Gorizia. In Austria la congiuntura generale 1880-1890 presenta aspetti di reale difficoltà, ma anche processi di trasformazione del vecchio apparato industriale ed evoluzioni positive del sistema finanziario. L'introduzione della Relazione… 1888 analizza le cause della crisi della struttura economica della Contea. A nostro parere al Presidente camerale, Eugenio Ritter, che percepisce, in ogni modo, importanti punti critici della situazione, sfuggono molte potenzialità provinciali: il suo sguardo indugia, forse eccessivamente, su Gorizia ed il suo circondario, senza riflettere sulle trasformazioni politiche ed economiche nel distretto gradiscano e nella bassa pianura. Le circoscrizioni di Cervignano, Cormons, Gradisca e Monfalcone sono in grado di rivaleggiare, alla fine del secolo XIX, con Gorizia ed il suo circondario in vari settori, in particolare nel tessile e nella lavorazione del legno. A Cormons sono attive filande e fabbriche di mobili, a Monfalcone e a Vermegliano, presso Ronchi, sono già operanti nel 1888 due importanti stabilimenti cotonieri, nel Cervignanese si rilevano fornaci di mattoni, filande e la famosa fabbrica d'amido del Chiozza. Per ragioni legate all'efficienza dei trasporti le nuove industrie prediligono le aree ben servite da infrastrutture come ferrovie e porti. Gorizia si presenta lontana rispetto ai principali assi di trasporto, almeno fino all'entrata in esercizio della Transalpina nel 1906, che ristabilisce, in parte e per breve tempo, l'equilibrio dei fattori a livello provinciale. Gli anni Novanta del secolo XIX sono, per l'Austria, il periodo della rinascita dopo la lunga stagnazione seguita alla crisi del 1873. Il governo centrale richiedeva pertanto la più ampia disponibilità possibile di dati statistici per valutare ed organizzare quello che si avviava a diventare, nei primi anni del Novecento, in modo certo imperfetto, uno dei più vasti mercati interni del periodo. Il Rapporto degli anni 1891-1895, tuttavia, è accomunato con il precedente nella valutazione negativa dell'evoluzione della struttura economica comitale. In realtà si tratta della crisi di un modello evolutivo imperniato sull'egemonia industriale del capoluogo. I fenomeni in atto a livello generale sono complessi e con diverse sfaccettature: si fanno sentire le prime avvisaglie della nuova rivoluzione produttiva, si affermano moderni metodi di raccolta e gestione dei capitali (le società per azioni, ad esempio), esplode il problema delle nazionalità. Questi processi si ripercuotono anche a livello locale, determinando una nuova distribuzione degli insediamenti produttivi. In quegli anni ha preminenza delle attività finanziarie in Austria ed in Europa innesca un processo che, senza eccessive forzature, si definisce di 'globalizzazione'. Le decisioni ed i progetti sono definiti ad alti livelli, scavalcando enti ed istituzioni locali, come succede alla piccola Camera goriziana. Nel quarto Capitolo tracciamo la storia delle mostre didattiche e l'istruzione professionale nel Goriziano a partire dal 1850 e principalmente con l'ausilio dei rapporti camerali summenzionati. Tra i fenomeni che caratterizzano la storia del periodo 1851-1914 va considerato particolarmente significativo il ruolo assunto dalle esposizioni universali in tutto il mondo industrializzato. Il 1851 è l'anno della prima esposizione mondiale, The Great Exhibition of the Works of Industry of All Nations, organizzata a Londra. Anche a Gorizia, fin dalla sua fondazione, la Camera di Commercio pose tra le sue finalità istituzionali primarie l'organizzazione di manifestazioni espositive, sia pure riferite al territorio provinciale. Dopo la chiusura della grande Esposizione mondiale di Vienna del 1873, un quotidiano locale scrisse che "Si può dire che gli oggetti degli espositori goriziani rappresentino genuinamente lo stato della nostra provincia: le grandi fabbriche e l'agricoltura sono rappresentate discretamente, l'industria minuta niente affatto; ed infatti è questo paese eminentemente agricolo e conta in pari tempo parecchi stabilimenti industriali, ma pur troppo sappiamo che i nostri artieri sono rimasti addietro di confronto anche a quelli dei paesi a noi limitrofi". La Camera di Commercio di Gorizia si profuse, da parte sua, per il miglioramento dell'istruzione insistendo sulla necessità dell'istituzione di una scuola professionale industriale, rivolgendo nello stesso anno 1873 una specifica domanda al Ministero. Anche nel Rapporto della Camera di Commercio pubblicato nel 1873, Ettore Ritter si sofferma a lungo sul problema dell'istruzione pubblica, a cui dedica un intero capitolo. La Scuola di perfezionamento, tuttavia, entra in funzione finalmente nel 1884, ormai sotto la tutela di Guglielmo Ritter, subentrato al fratello scomparso nella presidenza della Camera, e gestita anche con le contribuzioni del Governo, del Comune e della Dieta Provinciale. Si può dire che il 1887 segna il vero inizio della storia delle grandi mostre goriziane, cui seguiranno, fino alla prima guerra mondiale, almeno quattro manifestazioni importanti. Con gli anni Novanta, direttamente o indirettamente collegati all'attività della Camera di Commercio, il fenomeno delle mostre si diffonde anche a livello provinciale, in stretto rapporto con i corsi di formazione professionale organizzati già nel decennio precedente in diverse località. Vanno citate in particolare la scuola di perfezionamento per falegnami di Mariano e quella per panierai di Fogliano, istituite a sostegno di attività già piuttosto sviluppate. In realtà le mostre didattiche erano una consuetudine sviluppatasi in precedenza, in concomitanza con la riorganizzazione generale delle scuole avvenuta dopo la metà del secolo, e costituivano la tradizionale chiusura di tutti i corsi, a iniziare dalle scuole di disegno. La novità, per quanto riguarda le esposizioni didattiche di fine secolo, è rappresentata dal fatto che non vi compaiono solo i prodotti della scuola locale, ma, a titolo di esempio, oggetti provenienti da centri produttivi più avanzati o da un museo che organizzava mostre itineranti. Nei Capitoli 5 e 6, esaminando attentamente la documentazione E.N.A.P.I. dell'ASG, metto in rilievo la fondazione dell'Istituto per il Promovimento delle Industrie in Gorizia, la sua organizzazione e le sue attività nei primi anni. L'istituto per il Promovimento delle Industrie viene creato nel 1902 dalla Camera di Commercio di Gorizia sul modello dell'Ufficio per il Promovimento delle Industrie dell'i. r. Ministero del commercio di Vienna, esistente dal 1896. L'idea era stata lanciata dall'intraprendente segretario della Camera, Antonio Bisiach, e accolta con favore dai Presidenti Eugenio Ritter e Ludovico Mighetti, che ebbero pure l'appoggio del Comune, della Dieta Provinciale e delle autorità governative. Gestito da un Curatorio nel quale sono rappresentati tutti gli Enti sostenitori, l'Istituto opera dinamicamente fin dall'inizio e si propone ambiziosi compiti: informare gli industriali su nuovi strumenti e metodi produttivi, fungere da intermediario nei rapporti fra le industrie, appoggiare la formazione di consorzi e cooperative. Come si può leggere nella Relazione sull'attività spiegata fino alla fine di dicembre 1904, "il compito che si presentava al Curatorio, date le condizioni della provincia, non era facile, giacchè quella certa preparazione che trovasi fra il ceto operaio altrove manca nel Goriziano in gran parte." Ad aggravare questa situazione c'erano "l'indifferenza per i progressi moderni che si riscontra nella classe degli artieri" e la mancanza di scuole e musei industriali utili a istruire gli apprendisti. Nel programma dell'Istituto c'è prima di tutto un'articolata azione di sostegno dell'industria del legno, la più promettente, secondo il Curatorio, che comprende corsi di perfezionamento per falegnami (tenuti a Gorizia e a Cormons), esposizioni di mobili, aiuti alle cooperative; ma fin dall'inizio si organizzano anche corsi per calzolai a Monfalcone e Sesana, e si intraprende un'azione di valorizzazione della produzione dei cestai di Fogliano. I corsi sono diretti da insegnanti provenienti dall'Ufficio per il promovimento delle Industrie di Vienna, che svolgono una serie di lezioni teoriche (il corso per falegnami comprende: tecnologia, disegno professionale, disegno di dettaglio, meccanica, tenitura di libri e calcolazioni) e delle esercitazioni pratiche. I lavori sono, come sempre, oggetto dell'esposizione di chiusura. Tra il 1903 e il 1914 questa benemerita istituzione organizzò più di cento corsi d'istruzione professionale per ogni categoria di artigiani della provincia di Gorizia. Con il numero dei corsi tenuti nei paesi a maggioranza di lingua slovena e il numero dei partecipanti di lingua slovena, si mette in evidenza il fatto che l'Istituto organizzò vari corsi di perfezionamento, pur essendo tenuta la maggior parte dei corsi nella lingua tedesca, principalmente nelle città di Gorizia, Gradisca, Cormons ed altri paesi della pianura friulana di etnia italiana. Tali corsi di perfezionamento si tennero molto meno nei paesi di etnia slava come Caporetto, Comeno, Sesana e Merna. Fino al 1909 o 1910, furono prevalenti i partecipanti calzolai e falegnami. Dopo la fondazione di consorzi e cooperative, è possibile ipotizzare che questo nuovo sistema associativo sostituì il ruolo dell'Istituto e l'Istituto riuscì ad allargare le sue attività di istruzione ai nuovi campi, come ricamo e saldatura autogena, dopo il 1912. Sin dall'inizio delle attività dell'Istituto fu sempre presente la domanda di istruzione per sarti e pittori decoratori nel Goriziano. Per quanto riguarda i pittori decoratori, a Gorizia tale settore non fu mai presente fino a quell'epoca. Proprio per questa mancanza l'Istituto fondò una scuola speciale di perfezionamento per pittori, decoratori, verniciatori, indoratori ed arti affini, in Gorizia. Contemporaneamente vengono tenute decine di conferenze su svariati argomenti, organizzati viaggi d'istruzione e aperti ricreatori per apprendisti. Tra gli strumenti didattici una grande importanza continua ad essere data alle mostre, che assumono un carattere sempre più specialistico: nel 1907 una riservata all'industria edile, che riscuote un grande successo di pubblico, ed una rassegna d'arti grafiche in cui figurano tutte le migliori innovazioni della scuola viennese, illustrate anche in una conferenza; nel 1908, invece, torna l'interesse verso le arti tradizionali con una mostra di capolavori della pittura e scultura degli ultimi cento anni, organizzata in funzione della Scuola speciale di perfezionamento per pittori decoratori ed arti affini, sopra citato, aperta due anni prima. Anche in occasione di questa mostra si tengono conferenze illustrative che registrano una grande affluenza. L'Istituto per il Promovimento delle Industrie, con il suo dinamismo, l'attenzione concreta verso tutti i problemi connessi allo sviluppo dell'attività industriale, compresi quelli minuti inerenti le condizioni di vita della classe operaia, e, contemporaneamente, la sua proiezione in una dimensione europea, rappresenta certamente la migliore realizzazione dei progetti coltivati mezzo secolo prima da quel grande e lungimirante amministratore che era stato Ettore Ritter, il primo presidente della Camera di Commercio. Undici anni di attività bastano a dare a questo organismo un ruolo storico nel quadro generale dell'economia goriziana e a considerarlo meritevole di essere salvato anche dopo i grandi cambiamenti determinati dalla Grande Guerra. Secondo quanto si legge in una relazione del Comando militare italiano inviata nel 1917 al Segretariato Generale per gli affari civili della Provincia di Gorizia e Gradisca costituita dopo l'occupazione di Gorizia, "il risultato dell'attività dell'Istituto, date le difficili condizioni di sviluppo derivanti dall'antagonismo nazionale fomentato ad arte da cessato governo austriaco, è brillante. Ma migliore ancora sarà in avvenire, quando una concorde cooperazione degli enti locali e del Governo centrale di Roma, farà risorgere quest'istituzione, la quale, nata in Inghilterra anni addietro, fu trapiantata nelle nostre province, ove trovò terreno ferace per un prospero incremento, e più rigoglioso lo avrà quando sarà alimentato dalla genialità italica". ; XIX Ciclo

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ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

Bousquet, J; Hellings, P. W; Agache, I; Bedbrook, A; Bachert, C; Bergmann, K. C; Bewick, M; Bindslev-Jensen, C

Bousquet, J; Hellings, P. W; Agache, I; Bedbrook, A; Bachert, C; Bergmann, K. C; Bewick, M; Bindslev-Jensen, C; Bosnic-Anticevitch, S; Bucca, C; Caimmi, D. P; Camargos, P. A. M; Canonica, G. W; Casale, T; Chavannes, N. H; Cruz, A. A; De Carlo, G; Dahl, R; Demoly, P; Devillier, P; Fonseca, J; Fokkens, W. J; Guldemond, N. A; Haahtela, T; Illario, M; Just, J; Keil, T; Klimek, L; Kuna, P; Larenas-Linnemann, D; Morais-Almeida, M; Mullol, J; Murray, R; Naclerio, R; O'Hehir, R. E; Papadopoulos, N. G; Pawankar, R; Potter, P; Ryan, D; Samolinski, B; Schunemann, H. J; Sheikh, A; Simons, F. E. R; Stellato, C; Todo-Bom, A; Tomazic, P. V; Valiulis, A; Valovirta, E; Ventura, M. T; Wickman, M; Young, I; Yorgancioglu, A; Zuberbier, T; Aberer, W; Akdis, C. A; Akdis, M; Annesi-Maesano, I; Ankri, J; Ansotegui, I. J; Anto, J. M; Arnavielhe, S; Asarnoj, A; Arshad, H; Avolio, F; Baiardini, I; Barbara, C; Barbagallo, M; Bateman, E. D; Beghe, B; Bel, E. H; Bennoor, K. S; Benson, M; Bialoszewski, A. Z; Bieber, T; Bjermer, L; Blain, H; Blasi, F; Boner, A. L; Bonini, M; Bonini, S; Bosse, I; Bouchard, J; Boulet, L. P; Bourret, R; Bousquet, P. J; Braido, F; Briggs, A. H; Brightling, C. E; Brozek, J; Buhl, R; Bunu, C; Burte, E; Bush, A; Caballero-Fonseca, F; Calderon, M. A; Camuzat, T; Cardona, V; Carreiro-Martins, P; Carriazo, A. M; Carlsen, K. H; Carr, W; Cepeda Sarabia, A. M; Cesari, M; Chatzi, L; Chiron, R; Chivato, T; Chkhartishvili, E; Chuchalin, A. G; Chung, K. F; Ciprandi, G; Correia de Sousa, J; Cox, L; Crooks, G; Custovic, A; Dahlen, S. E; Darsow, U; Dedeu, T; Deleanu, D; Denburg, J. A; De Vries, G; Didier, A; Dinh-Xuan, A. T; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, S. R; Du Toit, G; Dykewicz, M. S; Eklund, P; El-Gamal, Y; Ellers, E; Emuzyte, R; Farrell, J; Wagner, A. Fink; Fiocchi, A; Fletcher, M; Forastiere, F; Gaga, M; Gamkrelidze, A; Gemicioglu, B; Gereda, J. E; van Wick, R. Gerth; Gonzalez Diaz, S; Grisle, I; Grouse, L; Gutter, Z; Guzman, M. A; Hellquist-Dahl, B; Heinrich, J; Horak, F; Hourihane, J. O'. B; Humbert, M; Hyland, M; Iaccarino, G; Jares, E. J; Jeandel, C; Johnston, S. L; Joos, G; Jonquet, O; Jung, K. S; Jutel, M; Kaidashev, I; Khaitov, M; Kalayci, O; Kalyoncu, A. F; Kardas, P; Keith, P. K; Kerkhof, M; Kerstjens, H. A. M; Khaltaev, N; Kogevinas, M; Kolek, V; Koppelman, G. H; Kowalski, M. L; Kuitunen, M; Kull, I; Kvedariene, V; Lambrecht, B; Lau, S; Laune, D; Le, L. T. T; Lieberman, P; Lipworth, B; Li, J; Carlsen, K. C. Lodrup; Louis, R; Lupinek, C; MacNee, W; Magar, Y; Magnan, A; Mahboub, B; Maier, D; Majer, I; Malva, J; Manning, P; De Manuel Keenoy, E; Marshall, G. D; Masjedi, M. R; Mathieu-Dupas, E; Maurer, M; Mavale-Manuel, S; Melen, E; Melo-Gomes, E; Meltzer, E. O; Mercier, J; Merk, H; Miculinic, N; Mihaltan, F; Milenkovic, B; Millot-Keurinck, J; Mohammad, Y; Momas, I; Mosges, R; Muraro, A; Namazova-Baranova, L; Nadif, R; Neffen, H; Nekam, K; Nieto, A; Niggemann, B; Nogueira-Silva, L; Nogues, M; Nyembue, T. D; Ohta, K; Okamoto, Y; Okubo, K; Olive-Elias, M; Ouedraogo, S; Paggiaro, P; Pali-Schoell, I; Palkonen, S; Panzner, P; Papi, A; Park, H. S; Passalacqua, G; Pedersen, S; Pereira, A. M; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Pohl, W; Popov, T. A; Portejoie, F; Postma, D; Poulsen, L. K; Price, D; Rabe, K. F; Raciborski, F; Roberts, G; Robalo-Cordeiro, C; Rodenas, F; Rodriguez-Manas, L; Rolland, C; Roman Rodriguez, M; Romano, A; Rosado-Pinto, J; Rosario, N; Rottem, M; Sanchez-Borges, M; Sastre-Dominguez, J; Scadding, G. K; Scichilone, N; Schmid-Grendelmeier, P; Serrano, E; Shields, M; Siroux, V; Sisul, J. C; Skrindo, I; Smit, H. A; Solé, Dirceu; Sooronbaev, T; Spranger, O; Stelmach, R; Sterk, P. J; Strandberg, T; Sunyer, J; Thijs, C; Triggiani, M; Valenta, R; Valero, A; van Eerd, M; van Ganse, E; van Hague, M; Vandenplas, O; Varona, L. L; Vellas, B; Vezzani, G; Vazankari, T; Viegi, G; Vontetsianos, T; Wagenmann, M; Walker, S; Wang, D. Y; Wahn, U; Werfel, T; Whalley, B; Williams, D. M; Williams, S; Wilson, N; Wright, J; Yawn, B. P; Yiallouros, P. K; Yusuf, O. M; Zaidi, A; Zar, H. J; Zernotti, M. E; Zhang, L; Zhong, N; Zidarn, M

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease. ; European Innovation Partnership ; Montpellier Univ Hosp, Montpellier, France ; European Innovat Partnership Act & Hlth Ageing Re, MAlad Chron Vleillissement Actif France, MACVIA France, Montpellier, France ; INSERM, Ageing & Chron Dis Epidemiol & Publ Hlth Approach, U1168, F-94800 Villejuif, France ; Katholieke Univ Leuven, Dept Microbiol & Immunol, Clin Immunol Lab, Louvain, Belgium ; Transylvania Univ Brasov, Brasov, Romania ; Ghent Univ Hosp, ENT Dept, Upper Airways Res Lab, Ghent, Belgium ; Charite, Dept Dermatol & Allergy, Allergy Ctr Charite, Berlin, Germany ; Global Allergy & Asthma European Network, Berlin, Germany ; iQ4U Consultants Ltd, London, England ; Odense Univ Hosp, Dept Dermatol, Odense, Denmark ; Odense Univ Hosp, Allergy Ctr, Odense, Denmark ; Univ Sydney & Sydney Local Hlth Dist, Woolcock Inst Med Res, Glebe, NSW, Australia ; Hosp City Hlth & Sci Torino, Univ Pneumol Unit AOU Molinette, Turin, Italy ; Montpellier Univ Hosp, Dept Resp Dis, Montpellier, France ; Univ Fed Minas Gerais, Dept Pediat, Sch Med, Belo Horizonte, MG, Brazil ; Humanitas Univ, Asthma & Allergy Clin, Milan, Italy ; Univ S Florida, Div Allergy Immunol, Tampa, FL USA ; Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands ; Univ Fed Bahia, ProAR Nucleo Excelencia Asma, Salvador, BA, Brazil ; GARD Execut Comm, Salvador, BA, Brazil ; EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium ; INSERM, EPAR U707, Paris, France ; Univ Paris 06, EPAR UMR S UPMC, Paris, France ; Suresnes Univ Versailles, Hop Foch, Lab Pharmacol Resp UPRES EA220, St Quentin en Yvelines, France ; Univ Porto, Ctr Res Hlth Technol & Informat Syst CINTESIS, Oporto, Portugal ; Inst CUF Porto, Allergy Unit, Oporto, Portugal ; Hosp CUF Porto, Oporto, Portugal ; Univ Porto, Fac Med, Hlth Informat & Decis Sci Dept CIDES, Rua Dr Placido da Costa S-N, P-4200450 Oporto, Portugal ; Acad Med Ctr, Dept Otorhinolaryngol, Amsterdam, Netherlands ; Erasmus Univ, Inst Hlth Policy & Management IBMG, Rotterdam, Netherlands ; Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland ; Univ Naples Federico II, Hosp Naples R&D & DISMET, Naples, Italy ; Univ Paris 06, UPMC,Equipe EPAR, Sorbonne Univ,Dept Allergol,Inst Pierre Louis Epi, Hopital Enfants Armand Trousseau,AP HP,Ctr Asthme, F-75013 Paris, France ; Charite, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany ; Univ Wurzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany ; Ctr Rhinol & Allergol, Wiesbaden, Germany ; Med Univ Lodz, Barlicki Univ Hosp, Div Internal Med Asthma & Allergy, Lodz, Poland ; Univ Barcelona, CIBERES, IDIBAPS, Hosp Clin,ENT Dept,Clin & Expt Resp Immunoallergy, M Barcelona, Catalonia, Spain ; Univ Chicago, Med Ctr, Sect Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA ; Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA ; Monash Univ, Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia ; Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia ; Monash Univ, Dept Immunol, Melbourne, Vic, Australia ; Univ Manchester, Royal Manchester Childrens Hosp, Inst Human Dev, Ctr Pediat & Child Hlth, Manchester, Lancs, England ; Univ Athens, Athens Gen Childrens Hosp P&A Kyriakou, Pediat Clin 2, Dept Allergy, Athens, Greece ; Nippon Med Sch, Dept Pediat, Tokyo, Japan ; Univ Cape Town, Lung Inst, Allergy Diagnost & Clin Res Unit, Cape Town, South Africa ; Woodbrook Med Ctr, Loughborough, Leics, England ; Univ Edinburgh, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland ; Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland ; McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada ; Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland ; Univ Manitoba, Fac Med, Dept Immunol, Dept Pediat & Child Hlth, Winnipeg, MB, Canada ; Univ Salerno, Div Allergy & Clin Immunol, Salerno, Italy ; Univ Coimbra, Fac Med, Ctr Pneumol, Coimbra, Portugal ; Med Univ Graz, Dept ENT, Graz, Austria ; Vilnius Univ, Fac Med, Clin Childrens Dis, Vilnius, Lithuania ; Vilnius Univ, Inst Publ Hlth, Vilnius, Lithuania ; European Acad Paediat EAP UEMS SP, Brussels, Belgium ; Univ Turku, Dept Lung Dis & Clin Allergol, Turku, Finland ; Terveystalo, Allergy Clin, Turku, Finland ; Univ Bari, Sch Med, Unit Geriatr Immunoallergol, Bari, Italy ; Soder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden ; Karolinska Inst, Inst Environm Med, Stockholm, Sweden ; Queens Univ, Belfast, Antrim, North Ireland ; Celal Bayar Univ, Dept Pulmonol, Manisa, Turkey ; Med Univ Graz, Dept Dermatol, Graz, Austria ; Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland ; Hosp Quiron Bizkaia, Dept Allergy & Immunol, Erandio, Spain ; Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain ; IMIM Hosp Mar Res Inst, Barcelona, Spain ; CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain ; Univ Pompeu Fabra, Barcelona, Spain ; Kyomed, Montpellier, France ; Karolinska Inst, Dept Med Solna, Clin Immunol & Allergy Unit, Stockholm, Sweden ; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Pediat Pulmonol & Allergy, Stockholm, Sweden ; David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England ; Reg Puglia, Bari, Italy ; Portuguese Natl Programme Resp Dis PNDR, Fac Med Lisbon, Lisbon, Portugal ; Univ Palermo, Dept Internal Med DIBIMIS, Geriatr Unit, Palermo, Italy ; Univ Cape Town, Dept Med, Cape Town, South Africa ; Univ Modena & Reggio Emilia, Dept Oncol Haematol & Resp Dis, Sect Resp Dis, Modena, Italy ; Univ Amsterdam, Acad Med Ctr, Dept Resp Med, Amsterdam, Netherlands ; Natl Inst Dis Chest & Hosp, Dept Resp Med, Dhaka, Bangladesh ; Linkoping Univ, Fac Med, Dept Pediat, Ctr Individualized Med, S-58185 Linkoping, Sweden ; Univ Bonn, Dept Dermatol & Allergy, Bonn, Germany ; Univ Hosp, Dept Resp Med & Allergol, Lund, Sweden ; Montpellier Univ Hosp, Dept Geriatr, BLAIN Montpellier, France ; Univ Montpellier, Euromov, EA 2991, Montpellier, France ; Univ Milan, IRCCS Fdn CaGranda Osped Maggiore Policlin, Dept Pathophysiol & Transplantat, Milan, Italy ; Univ Verona Hosp, Dept Pediat, Verona, Italy ; Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Rome, Italy ; Univ Naples 2, Naples, Italy ; Italian Natl Res Council, Inst Translat Med, Naples, Italy ; Univ Laval, Quebec Heart & Lung Inst, Quebec City, PQ, Canada ; Univ Glasgow, Inst Hlth & Wellbeing, Hlth Econ & Hlth Technol Assessment, Glasgow, Lanark, Scotland ; Univ Hosp Leicester NHS Trust, Inst Lung Hlth, Resp Biomed Unit, Leicester, Leics, England ; Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England ; Johannes Gutenberg Univ Mainz, Univ Med, Mainz, Germany ; Univ Med & Farm Timisoara, Timisoara, Romania ; Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp NHS, London, England ; Ctr Med Docente Trinidad, Caracas, Venezuela ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England ; Reg Languedoc Roussillon, Montpellier, France ; Hosp Valle De Hebron, S Allergol S Med Interna, Barcelona, Spain ; CEDOC, Resp Res Grp, Nova Med Sch, Lisbon, Portugal ; Ctr Hosp Lisboa Cent, EPE, Serv Imunoalergol, Lisbon, Portugal ; Reg Minist Hlth Andalusia, Seville, Spain ; Oslo Univ Hosp, Dept Paediat, Oslo, Norway ; Univ Oslo, Oslo, Norway ; Allergy & Asthma Associates Southern Calif, Mission Viejo, CA USA ; Metropolitan Univ, Univ Simon Bolivar, Allergy & Immunol Lab, Barranquilla, Colombia ; SLaai Sociedad Latinoamer Allergia Asma & Immunol, Cartagena, Colombia ; Gerontopole Toulouse, F-31059 Toulouse, France ; Univ Crete, Fac Med, Dept Social Med, Iraklion, NE, Greece ; Univ CEU San Pablo, Sch Med, Madrid, Spain ; Grigol Robakidze Univ, David Tvildiani Med Univ, AIETI Med Sch, Chachava Clin, Tbilisi, Rep of Georgia ; Pulmonolory Res Inst FMBA, Moscow, Russia ; GARD Execut Comm, Moscow, Russia ; IRCCS Azienda Osped Univ San Martino, Dept Med, Genoa, Italy ; Univ Minho, Sch Hlth Sci, Res Inst ICVS, ICVS 3BsPT Govt Associate Lab,Life & Hlth Sci, Braga, Portugal ; Nova Southeastern Univ, Dept Med, Davie, FL USA ; Scottish Ctr Telehealth & Telecare, NHS 24, European Innovat Partnership Act & Hlth Ageing, Reference Site,EIP AHA, Glasgow, Lanark, Scotland ; Univ London Imperial Coll Sci Technol & Med, Dept Pediat, London, England ; Karolinska Inst, Inst Environm Med, Ctr Allergy Res, Stockholm, Sweden ; Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany ; Helmholtz Ctr Munich, ZAUM Ctr Allergy & Environm, Munich, Germany ; AQuAS, Barcelona, Spain ; European Reg & Local Hlth Assoc, EUREGHA, Brussels, Belgium ; Luliu Hatieganu Univ Med & Pharm, Allergol & Immunol Discipline, Cluj Napoca, Romania ; McMaster Univ, Dept Med, Div Clin Immunol & Allergy, Hamilton, ON, Canada ; Peercode DV, Amsterdam, Netherlands ; Rangueil Larrey Hosp, Dept Resp Dis, Toulouse, France ; Univ Paris 05, Hop Cochin, AP HP, Serv Physiol Resp, Paris, France ; Ss Cyril & Methodius Univ, Fac Med, Univ Clin Pulmol & Allergy, Skopje, Macedonia ; Ctr Hosp Univ Beni Messous, Serv Pneumoallergol, Algiers, Algeria ; Ecole Mines, Ales, France ; Vilnius Univ, Fac Med, Vilnius, Lithuania ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Allergy & Clin Immunol Sect, London, England ; Kings Coll London, Guys & St Thomas NHS Trust, London, England ; St Louis Univ, Sch Med, Sect Allergy & Immunol, St Louis, MO USA ; Umea Univ, Dept Comp Sci, Umea, Sweden ; Four Comp Oy, Halikko, Finland ; Ain Shams Univ, Pediat Allergy & Immunol Unit, Cairo, Egypt ; Social Serv & Publ Safety, Dept Hlth, Belfast, Antrim, North Ireland ; Global Allergy & Asthma Platform, Altgasse 8-10, A-1130 Vienna, Austria ; Bambino Gesu Childrens Res Hosp Holy See, Dept Pediat Med, Div Allergy, Rome, Italy ; Educ Hlth, Warwick, England ; Reg Hlth Serv Lazio Reg, Dept Epidemiol, Rome, Italy ; Athens Chest Hosp, Athens, Greece ; Natl Ctr Dis Control & Publ Hlth Georgia, Tbilisi, Rep of Georgia ; Istanbul Univ, Cerrahpasa Fac Med, Dept Pulm Dis, Istanbul, Turkey ; Clin Ricardo Palma, Allergy & Immunol Div, Lima, Peru ; Erasmus MC, Dept Internal Med, Sect Allergol, Rotterdam, Netherlands ; Univ Autonoma Nuevo Leon, San Nicolas De Los Garza, Mexico ; Latvian Assoc Allergists, Ctr TB & Lung Dis, Riga, Latvia ; Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA ; Univ Hosp Olomouc, Natl eHlth Ctr, Olomouc, Czech Republic ; Univ Chile, Clin Hosp, Immunol & Allergy Div, Santiago, Chile ; Odense Univ Hosp, Dept Resp Dis, Odense, Denmark ; German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany ; Vienna Challenge Chamber, Vienna, Austria ; Univ Coll Cork, Dept Paediat & Child Hlth, Cork, Ireland ; Univ Paris 11, Le Kremlin Bicetre, France ; Hop Bicetre, Serv Pneumol, Le Kremlin Bicetre, France ; INSERM, UMR S999, Le Kremlin Bicetre, France ; Univ Plymouth, Sch Psychol, Plymouth, Devon, England ; Univ Salerno, Dept Med & Surg, Baronissi, Italy ; Libra Fdn, Buenos Aires, DF, Argentina ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, London, England ; MRC & Asthma UK Ctr Allerg Mech Asthma, London, England ; Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium ; Montpellier Univ Hosp, Med Commiss, Montpellier, France ; Hallym Univ, Coll Med, Hallym Univ Sacred Heart Hosp, Anyang, Gyeonggi Do, South Korea ; Wroclaw Med Univ, Dept Clin Immunol, Wroclaw, Poland ; Ukrainian Med Stomatol Acad, Poltava, Ukraine ; Fed Medicobiol Agcy, Inst Immunol, Natl Res Ctr, Lab Mol Immunol, Moscow, Russia ; Hacettepe Univ, Sch Med, Pediat Allergy & Asthma Unit, Ankara, Turkey ; Hacettepe Univ, Sch Med, Dept Chest Dis, Immunol & Allergy Div, Ankara, Turkey ; Med Univ Lodz, Dept Family Med 1, Lodz, Poland ; McMaster Univ, Dept Med, Hlth Sci Ctr 3V47, 1280 Main St W, Hamilton, ON, Canada ; Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Dis, Groningen, Netherlands ; GARD, Geneva, Switzerland ; Univ Hosp Olomouc, Fac Med & Dent, Dept Resp Med, Olomouc, Czech Republic ; Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Beatrix Childrens Hosp,Dept Pediat Pulmonol & Ped, Groningen, Netherlands ; Med Univ Lodz, Deptment Immunol Rheumatol & Allergy & HARC, Lodz, Poland ; Univ Helsinki, Childrens Hosp, Helsinki, Finland ; Vilnius Univ, Clin Infect Chest Dis Dermatol & Allergol, Vilnius, Lithuania ; Univ Ghent, VIB Inflammat Res Ctr, Ghent, Belgium ; Charite, Dept Pediat Pneumol & Immunol, Berlin, Germany ; Univ Med & Pharm, Hochiminh City, Vietnam ; Univ Tennessee, Coll Med, Dept Internal Med & Pediat, Div Allergy & Immunol, Germantown, TN USA ; Univ Dundee, Ninewells Hosp, Med Res Inst, Scottish Ctr Resp Res Cardiovasc & Diabet Med, Dundee, Scotland ; Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China ; Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway ; CHU Sart Tilman, Dept Pulm Med, Liege, Belgium ; Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Div Immunopathol, Vienna, Austria ; Univ Edinburgh, Queens Med Res Inst, Edinburgh, Midlothian, Scotland ; Hop St Joseph, Serv Pneumoallergol, Paris, France ; Univ Nantes, UMR INSERM, Serv Pneumol, UMR1087, Nantes, France ; Univ Nantes, Inst Thorax, CNR 6291, Nantes, France ; Rashid Hosp, Dept Pulm Med, Dubai, U Arab Emirates ; Biomax Informat AG, Munich, Germany ; Univ Bratislava, Dept Resp Med, Bratislava, Slovakia ; Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci, Coimbra, Portugal ; Ageing@Coimbra EIP AHA Reference Site, Coimbra, Portugal ; Bon Secours Hosp, Dept Med, Dublin, Ireland ; Kronikgune, Basque Region, Spain ; Univ Mississippi, Med Ctr, Div Clin Immunol & Allergy, Lab Behav Immunol Res, Jackson, MS USA ; Iranian Anti Tobacco Assoc, Tobacco Control Res Ctr, Tehran, Iran ; Maputo Cent Hosp, Dept Paediat, Maputo, Mozambique ; Allergy & Asthma Med Grp & Res Ctr, San Diego, CA USA ; Univ Montpellier, Dept Physiol, CHRU, PhyMedExp,INSERM U1046,CNRS UMR 9214, Montpellier, France ; Rhein Westfal TH Aachen, Univ Klinikum, Hautklin Klin Dermatol & Allergol, Aachen, Germany ; Croatian Pulm Soc, Zagreb, Croatia ; Natl Inst Pneumol M Nasta, Bucharest, Romania ; Univ Belgrade, Fac Med, Belgrade, Serbia ; Serbian Assoc Asthma & COPD, Belgrade, Serbia ; Caisse Assurance Retraite & Sante Travail Langued, Montpellier, France ; Tishreen Univ, Sch Med, Natl Ctr Res Chron Resp Dis, Latakia, Syria ; Paris Descartes Univ, Sorbonne Paris Cite, Dept Publ Hlth & Hlth Prod, EA 4064, Paris, France ; Paris Municipal Dept Social Act Childhood & Hlth, Paris, France ; Univ Cologne, Fac Med, Inst Med Stat Informat & Epidemiol, Cologne, Germany ; Padua Gen Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr Veneto Reg, Padua, Italy ; Russian Acad Med Sci, Sci Ctr Childrens Hlth, Moscow, Russia ; Hosp Ninos Orlando Alassia, Santa Fe, Argentina ; Hosp Hosp Bros Buda, Budapest, Hungary ; Hosp La Fe, Neumol & Alergol Infantil, Valencia, Spain ; Ctr Hosp Sao Joao, Dept Internal Med, Oporto, Portugal ; Univ Hosp Kinshasa, ENT Dept, Kinshasa, DEM REP CONGO ; Tokyo Natl Hosp, Natl Hosp Org, Tokyo, Japan ; Chiba Univ Hosp, Dept Otorhinolaryngol, Chiba, Japan ; Nippon Med Sch, Dept Otolaryngol, Tokyo, Japan ; Ctr Hosp Univ Pediatr Charles Gaulle, Ouagadougou, Burkina Faso ; Univ Hosp Pisa, Cardiothorac & Vasc Dept, Pisa, Italy ; Med Univ, Univ Vet Med, Messerli Res Inst, Dept Comparat Med, Vienna, Austria ; Charles Univ Prague, Fac Med, Dept Immunol & Allergol, Plzen, Czech Republic ; Charles Univ Prague, Fac Hosp Pilsen, Plzen, Czech Republic ; Univ Ferrara, Dept Med Sci, Resp Med, Ferrara, Italy ; Ajou Univ, Sch Med, Dept Allergy & Clin Immunol, Suwon, South Korea ; Univ Southern Denmark, Kolding, Denmark ; CUF Porto Hosp & Inst, Allergy Unit, Oporto, Portugal ; Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Otorhinolaryngol Head & Neck Surg, Mannheim, Germany ; Minist Econ Ind & Numer, Conseil Gen Econ, Paris, France ; Espace Francophone Pneumol, Soc Pneumol Langue Francaise, Paris, France ; CHU Grenoble, Dept Pediat, Grenoble, France ; Childrens Hosp Srebrnjak, Zagreb, Croatia ; Univ JJ Strossmayer, Sch Med, Osijek, Croatia ; Hietzing Hosp, Karl Landsteiner Inst Clin & Expt Pneumol, Vienna, Austria ; Med Univ Sofia, Clin Allergy & Asthma, Sofia, Bulgaria ; Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands ; Copenhagen Univ Hosp Gentofte, Allergy Clin, Lab Med Allergol, Copenhagen, Denmark ; Univ Aberdeen, Acad Ctr Primary Care, Aberdeen, Scotland ; Res Real Life, Cambridge, England ; German Ctr Lung Res DZL, Airway Res Ctr North, LungenClin Grosshansdorf, Grosshansdorf, Germany ; Univ Kiel, German Ctr Lung Res DZL, Airway Res Ctr North, Dept Med, Kiel, Germany ; Southampton Univ Hosp, NHS Fdn Trust, Southampton, Hants, England ; Coimbra Univ Hosp, Ctr Pneumol, Coimbra, Portugal ; Univ Valencia, Polibienestar Res Inst, Valencia, Spain ; Getafe Univ Hosp, Dept Geriatr, Madrid, Spain ; Assoc Asthme & Allergie, Paris, France ; Inst Invest Sanitaria Palma IdisPa, Primary Care Resp Res Unit, Palma De Mallorca, Spain ; Complesso Integrato Columbus, Allergy Unit, Rome, Italy ; Hosp Luz, Serv Imunoalergol, Lisbon, Portugal ; Univ Parana, Hosp Clin, Curitiba, Parana, Brazil ; Emek Med Ctr, Div Allergy Asthma & Clin Immunol, Afula, Israel ; Ctr Med Docente Trinidad & Clin El Avila, Allergy & Clin Immunol Dept, Caracas, Venezuela ; Autononous Univ Madrid, Fac Med, Madrid, Spain ; UCL, Royal Natl TNE Hosp, London, England ; Univ Palermo, DIBIMIS, Palermo, Italy ; Univ Zurich Hosp, Dept Dermatol, Allergy Unit, Zurich, Switzerland ; CHU Rangueil Larrey, Otolaryngol & Head & Neck Surg, Toulouse, France ; Queens Univ, Child Hlth, Belfast, Antrim, North Ireland ; Royal Belfast Hosp Sick Children, Belfast, Antrim, North Ireland ; Univ Joseph Fourier, Team Environm Epidemiol Appl Reprod & Resp Hlth, Univ Grenoble Alpes, INSERM,IAB U 1209, Grenoble, France ; Soc Paraguaya Alergia Asma & Inmunol, Asuncion, Paraguay ; Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands ; Univ Fed Sao Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, Sao Paulo, Brazil ; Euro Asian Resp Soc, Kyrgyzstan Natl Ctr Cardiol & Internal Med, Bishkek, Kyrgyzstan ; Univ Sao Paulo, Fac Med, Hosp Clin, Div Pulm,Inst Heart InCor, Sao Paulo, Brazil ; Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands ; European Union Geriatr Med Soc EUGMS, Helsinki, Finland ; Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Epidemiol, Maastricht, Netherlands ; IDIBAPS, Hosp Clin, Pneumol & Allergy Dept, Clin & Expt Resp Immunoallergy, Barcelona, Spain ; PELyon, Lyon, France ; Univ Claude Bernard Lyon, Hlth Serv & Performance Res, HESPER 7425, Villeurbanne, France ; Univ Hosp, Stockholm, Sweden ; Catholic Univ Louvain, Univ UCL Namur, Ctr Hosp Univ UCL Namur, Dept Chest Med, Yvoir, Belgium ; Philippines Soc Allergy Asthma & Immunol, Manila, Philippines ; Res Hosp, Arcispedale S Maria Nuova IRCCS, Dept Cardiol Thorac & Vasc Med, Pulm Unit, Reggio Emilia, Italy ; Reg Agcy Hlth & Social Care, Reggio Emilia, Italy ; Finnish Lung Assoc FILHA, Helsinki, Finland ; CNR Inst Clin Physiol, Pulm Environm Epidemiol Unit, Pisa, Italy ; CNR, Inst Biomed & Mol Immunol A Monroy, Palermo, Italy ; Sotiria Hosp, Athens, Greece ; Univ Klinikum Dusseldorf, HNO Klin, Dept Otorhinolaryngol, Dusseldorf, Germany ; Asthma UK, Mansell St, London, England ; Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Otolaryngol, Singapore, Singapore ; Hannover Med Sch, Dept Dermatol & Allergy, Div Immunodermatol & Allergy Res, Hannover, Germany ; Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA ; IPCRG, Aberdeen, Scotland ; Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England ; Olmsted Med Ctr, Dept Res, Rochester, MN USA ; Univ Cyprus, Sch Med, Nicosia, Cyprus ; Allergy & Asthma Inst, Lahore, Pakistan ; Univ Southampton, Social Sci, Southampton, Hants, England ; Univ Cape Town, Red Cross Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa ; Univ Cape Town, MRC Unit Child & Adolescent Hlth, Cape Town, South Africa ; Univ Catolica Cordoba, Cordoba, Argentina ; Beijing TongRen Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China ; Beijing Inst Otolaryngol, Beijing, Peoples R China ; Univ Clin Resp & Allerg Dis, Golnik, Slovenia ; Northern Hlth Alliance, Newcastle Upon Tyne, Tyne & Wear, England ; CHRU Arnaud Villeneuve, 371 Ave Doyen Gaston Giraud, Montpellier 5, France ; Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil ; Web of Science

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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Coignard, Juliette; Lush, Michael; Beesley, Jonathan; O'Mara, Tracy A; Dennis, Joe; Tyrer, Jonathan P; Barnes, Daniel R; McGuffog, Lesley

Coignard, Juliette; Lush, Michael; Beesley, Jonathan; O'Mara, Tracy A; Dennis, Joe; Tyrer, Jonathan P; Barnes, Daniel R; McGuffog, Lesley; Leslie, Goska; Bolla, Manjeet K; Adank, Muriel A; Agata, Simona; Ahearn, Thomas; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arnold, Norbert; Aronson, Kristan J; Arun, Banu K; Augustinsson, Annelie; Azzollini, Jacopo; Barrowdale, Daniel; Baynes, Caroline; Becher, Heiko; Bermisheva, Marina; Bernstein, Leslie; Białkowska, Katarzyna; Blomqvist, Carl; Bojesen, Stig E; Bonanni, Bernardo; Borg, Ake; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldés, Trinidad; Caligo, Maria A; Campa, Daniele; Carter, Brian D; Castelao, Jose E; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Clarke, Christine L; Collée, J Margriet; Conroy, Don M; Czene, Kamila; Daly, Mary B; Devilee, Peter; Diez, Orland; Ding, Yuan Chun; Domchek, Susan M; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Dwek, Miriam; Eccles, Diana M; Eliassen, A Heather; Engel, Christoph; Eriksson, Mikael; Evans, D Gareth; Fasching, Peter A; Flyger, Henrik; Fostira, Florentia; Friedman, Eitan; Fritschi, Lin; Frost, Debra; Gago-Dominguez, Manuela; Gapstur, Susan M; Garber, Judy; Garcia-Barberan, Vanesa; García-Closas, Montserrat; García-Sáenz, José A; Gaudet, Mia M; Gayther, Simon A; Gehrig, Andrea; Georgoulias, Vassilios; Giles, Graham G; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; Gonzalez Neira, Anna; Greene, Mark H; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A; Håkansson, Niclas; Hall, Per; Hamann, Ute; Harrington, Patricia A; Hart, Steven N; He, Wei; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Horcasitas, Darling J; Hulick, Peter J; Hunter, David J; Imyanitov, Evgeny N; Jager, Agnes; Jakubowska, Anna; James, Paul A; Jensen, Uffe Birk; John, Esther M; Jones, Michael E; Kaaks, Rudolf; Kapoor, Pooja Middha; Karlan, Beth Y; Keeman, Renske; Khusnutdinova, Elza; Kiiski, Johanna I; Ko, Yon-Dschun; Kosma, Veli-Matti; Kraft, Peter; Kurian, Allison W; Laitman, Yael; Lambrechts, Diether; Le Marchand, Loic; Lester, Jenny; Lesueur, Fabienne; Lindstrom, Tricia; Lopez-Fernández, Adria; Loud, Jennifer T; Luccarini, Craig; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Martens, John W M; Mebirouk, Noura; Meindl, Alfons; Miller, Austin; Milne, Roger L; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nielsen, Finn C; O'Brien, Katie M; Olopade, Olufunmilayo I; Olson, Janet E; Olsson, Håkan; Osorio, Ana; Ottini, Laura; Park-Simon, Tjoung-Won; Parsons, Michael T; Pedersen, Inge Sokilde; Peshkin, Beth; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D P; Phillips, Kelly-Anne; Polley, Eric C; Poppe, Bruce; Presneau, Nadege; Pujana, Miquel Angel; Punie, Kevin; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad U; Rennert, Gad; Rennert, Hedy S; Robson, Mark; Romero, Atocha; Rossing, Maria; Saloustros, Emmanouil; Sandler, Dale P; Santella, Regina; Scheuner, Maren T; Schmidt, Marjanka K; Schmidt, Gunnar; Scott, Christopher; Sharma, Priyanka; Soucy, Penny; Southey, Melissa C; Spinelli, John J; Steinsnyder, Zoe; Stone, Jennifer; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Tamimi, Rulla M; Tapper, William J; Taylor, Jack A; Terry, Mary Beth; Teulé, Alex; Thull, Darcy L; Tischkowitz, Marc; Toland, Amanda E; Torres, Diana; Trainer, Alison H; Truong, Thérèse; Tung, Nadine; Vachon, Celine M; Vega, Ana; Vijai, Joseph; Wang, Qin; Wappenschmidt, Barbara; Weinberg, Clarice R; Wendt, Camilla; Weitzel, Jeffrey N; Wolk, Alicja; Yadav, Siddhartha; Yang, Xiaohong R; Yannoukakos, Drakoulis; Zheng, Wei; Ziogas, Argyrios; Zorn, Kristin K; Park, Sue K; Thomassen, Mads; Offit, Kenneth; Schmutzler, Rita K; Couch, Fergus J; Simard, Jacques; Chenevix-Trench, Georgia; Easton, Douglas F; Andrieu, Nadine; Antoniou, Antonis C

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. ; BCAC acknowledgements. 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, Gillian Dite. ABCS thanks the Blood bank Sanquin, The Netherlands. ABCTB Investigators: Christine Clarke, Deborah Marsh, Rodney Scott, Robert Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter Simpson, J. Dinny Graham, Mythily Sachchithananthan. Samples are made available to researchers on a non-exclusive basis. BBCS thanks Eileen Williams, Elaine Ryder-Mills, Kara Sargus. 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. 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 Munoz Garzon, Alejandro Novo Dominguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Pena Fernandez, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), Jose Antunez, Maximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigacion Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquin Gonzalez-Carrero 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 Kjeldgard Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. CNIO-BCS thanks Guillermo Pita, Charo Alonso, Nuria alvarez, Pilar Zamora, Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO). 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. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Krober and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tubingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tubingen [[HB], gefordert durch die Deutsche Forschungsgemeinschaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Lander - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [YDK, 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 [Thomas Bruning, 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 Kirsimari Aaltonen, Irja Erkkila. HUBCS thanks Shamil Gantsev. KARMA and SASBAC thank the Swedish Medical Research Counsel. KBCP thanks Eija Myohanen, Helena Kemilainen. kConFab/AOCS wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab 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. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. 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): Mariarosaria Calvello, Davide Bondavalli, Aliana Guerrieri Gonzaga, Monica Marabelli, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. The MCCS was made possible by the contribution of many people, including the original investigators, the teams that recruited the participants and continue working on follow-up, and the many thousands of Melbourne residents who continue to participate in the study. 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, Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Quebec - Universite Laval 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 skilful technical assistance. J.S. is Chair holder of the Canada Research Chair in Oncogenetics. NBHS and SBCGS thank study participants and research staff for their contributions and commitment to the studies. For NHS and NHS2 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. We would like to thank the participants and staff of the NHS and NHS2 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., and W.Y. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander, 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, 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. RBCS thanks Jannet Blom, Saskia Pelders, Annette Heemskerk and 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. 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. We acknowledge funding to the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. CIMBA acknowledgments. All the families and clinicians who contribute to the studies; Catherine M. Phelan for her contribution to CIMBA until she passed away on 22 September 2017; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Gillian Dite, 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 Grikeviius; Drs Janis Eglitis, Anna Krilova and Aivars Stengrevics; 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), in particular: Bernard Peissel, Dario Zimbalatti, Daniela Zaffaroni, Alessandra Viel, Giuseppe Giannini Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. Ms. JoEllen Weaver and Dr. Betsy Bove; FPGMX: members of the Cancer Genetics group (IDIS): Marta Santamarina, Miguel Aguado and Olivia Rios; IFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber); 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 (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, Melanie Leone, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valerie 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: Coordinating Centre, Service de Genetique, Institut Curie, Paris, France: Muriel Belotti, Ophelie Bertrand, Anne-Marie Birot, Bruno Buecher, Sandrine Caputo, Anais Dupre, Emmanuelle Fourme, Marion Gauthier-Villars, Lisa Golmard, Claude Houdayer, Marine Le Mentec, Virginie Moncoutier, Antoine de Pauw, Claire Saule, Dominique Stoppa-Lyonnet, and Inserm U900, Institut Curie, Paris, France: Fabienne Lesueur, Noura Mebirouk. Contributing Centres: Unite Mixte de Genetique Constitutionnelle des Cancers Frequents, Hospices Civils de Lyon - Centre Leon Berard, Lyon, France: Nadia Boutry-Kryza, Alain Calender, Sophie Giraud, Melanie Leone. Institut Gustave Roussy, Villejuif, France: Brigitte Bressac-de-Paillerets, Olivier Caron, Marine Guillaud-Bataille. Centre Jean Perrin, Clermont-Ferrand, France: Yves-Jean Bignon, Nancy Uhrhammer. Centre Leon Berard, Lyon, France: Valerie Bonadona, Christine Lasset. Centre Francois Baclesse, Caen, France: Pascaline Berthet, Laurent Castera, Dominique Vaur. Institut Paoli Calmettes, Marseille, France: Violaine Bourdon, Catherine Nogues, Tetsuro Noguchi, Cornel Popovici, Audrey Remenieras, Hagay Sobol. CHU Arnaud-de-Villeneuve, Montpellier, France: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille, France: Claude Adenis, Aurelie Dumont, Francoise Revillion. Centre Paul Strauss, Strasbourg, France: Daniele Muller. Institut Bergonie, Bordeaux, France: Emmanuelle Barouk-Simonet, Francoise Bonnet, Virginie Bubien, Michel Longy, Nicolas Sevenet, Institut Claudius Regaud, Toulouse, France: Laurence Gladieff, Rosine Guimbaud, Viviane Feillel, Christine Toulas. CHU Grenoble, France: Helene Dreyfus, Christine Dominique Leroux, Magalie Peysselon, Rebischung. CHU Dijon, France: Amandine Baurand, Geoffrey Bertolone, Fanny Coron, Laurence Faivre, Caroline Jacquot, Sarab Lizard. CHU St-Etienne, France: Caroline Kientz, Marine Lebrun, Fabienne Prieur. Hotel Dieu Centre Hospitalier, Chambery, France: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice, France: Veronique Mari. CHU Limoges, France: Laurence Venat-Bouvet. CHU Nantes, France: Stephane Bezieau, Capucine Delnatte. CHU Bretonneau, Tours and Centre Hospitalier de Bourges France: Isabelle Mortemousque. Groupe Hospitalier Pitie-Salpetriere, Paris, France: Chrystelle Colas, Florence Coulet, Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les-Nancy, France: Myriam Bronner, Johanna Sokolowska. CHU Besancon, France: Marie-Agnes Collonge-Rame, Alexandre Damette. CHU Poitiers, Centre Hospitalier d'Angouleme and Centre Hospitalier de Niort, France: Paul Gesta. Centre Hospitalier de La Rochelle: Hakima Lallaoui. CHU Nimes Caremeau, France: Jean Chiesa. CHI Poissy, France: Denise Molina-Gomes. CHU Angers, France: Olivier Ingster; Ilse Coene en Brecht Crombez; Ilse Coene and Brecht Crombez; Alicia Tosar and Paula Diaque; Drs.Sofia Khan, Taru A. Muranen, Carl Blomqvist, Irja Erkkila and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collee, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, 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, R.B. van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M. Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, NL: E.B. Gomez-Garcia, M.J. Blok; University Medical Center Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer Organization (IKNL): S. Siesling, J.Verloop; 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; Ana Peixoto, 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 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; Leigha Senter, Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O'Conor; HVH: acknowledgments to the Cellex Foundation for providing research facilities and equipment. Dr Juliette Coignard was supported by a fellowship of INCa Institut National du Cancer N degrees 2015-181, la Ligue Nationale contre le Cancer IP/SC-15229 and Olga Sinilnikova's fellowship (2016). BCAC Funding. 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 Communitys 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 Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec 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 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, 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. The BREast Oncology GAlician Network (BREOGAN) is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Accion Estrategica 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, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica 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). 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 Securite 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 Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). 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. 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 Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (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 Andalucia, 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 Wurttemberg 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). 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 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 UniversityHospital Research Fund, the Finnish Cancer Society, and the Sigrid Juselius 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. 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 Marit 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. 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. LMBC is supported by the 'Stichting tegen Kanker'. 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; IG2014 no.15547) to P. Radice. 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. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, 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. 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 (VR 2017-00644) grant for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER). The SZBCS and IHCC were supported by Grant PBZ_KBN_122/P05/2004 and the program of the Minister of Science and Higher Education under the name Regional Initiative of Excellence in 2019-2022 project number 002/RID/2018/19 amount of financing 12 000 000 PLN. 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. 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. CIMBA Funding. CIMBA: The CIMBA data management and data analysis were supported by Cancer Research - UK grants C12292/A20861, C12292/A11174. 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 Quebec, 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. BIDMC: Breast Cancer Research Foundation. 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: 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') to S. Manoukian. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. 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. DKFZ: 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: A.K.G. was in part funded by the NCI (R01 CA214545), The University of Kansas Cancer Center Support Grant (P30 CA168524), The Kansas Institute for Precision Medicine (P20 GM130423), and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Professorship. A.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 Investigacion Biomedica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundacion Mutua Madrilena (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 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, 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. HEBON thanks the registration teams of Dutch Cancer Registry (IKNL; S. Siesling, J. Verloop) and the Dutch Pathology database (PALGA; L. Overbeek) for part of the data collection. ICO: The authors would like to particularly acknowledge the support of the Asociacion Espanola Contra el Cancer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economia 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 Catala de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). 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. 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 17-00-00171, 18-515-45012 and 19-515-25001). 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 Tumours (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. UPENN: 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. HVH: Supported by the Carlos III National Health Institute funded by FEDER funds - a way to build Europe - PI16/11363. MT Parsons is supported by a grant from Newcastle University. Kelly-Anne Phillips is an Australian National Breast Cancer Foundation Fellow. ; Sí

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Open Access#8482019

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Figlioli, Gisella; Agnarsson, Bjarni A; Barkardottir, Rosa Bjork

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

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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline B; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline B; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J; Li, Qiyuan; Delgado, Melissa K; Lee, Janet M; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Bandera, Elisa V; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Matthias W; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B M; Cook, Linda S; Cox, Angela; Cramer, Daniel W; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Engel, Christoph; Lee, Eunjung; Evans, D Gareth; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D; Fridley, Brooke L; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G; Glasspool, Rosalind; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira A, Anna; Goode, Ellen L; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Harrington, Patricia A; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Hulick, Peter J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y; Khan, Sofia; Kiemeney, Lambertus A; Kjaer, Susanne Kruger; Knight, Julia A; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F A G; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R; Milne, Roger L; Montagna, Marco; Moysich, Kirsten B; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poole, Elizabeth M; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Sellers, Thomas A; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F; Sinilnikova, Olga M; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tung, Nadine; Tworoger, Shelley S; Vachon, Celine; van den Ouweland, Ans M W; van Doorn, Helena C; van Rensburg, Elizabeth J; Van't Veer, Laura J; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Wildiers, Hans; Winqvist, Robert; Wu, Anna H; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N; French, Juliet D; Couch, Fergus J; Freedman, Matthew L; Easton, Douglas F; Dunning, Alison M; Pharoah, Paul D; Edwards, Stacey L; Chenevix-Trench, Georgia; Antoniou, Antonis C; Gayther, Simon A

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. ; We thank all the individuals who took part in these studies and all the researchers, clin- icians, technicians and administrative staff who have enabled this work to be carried out, in particular those involved in the COGS project: Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, the staff of the CNIO genotyping unit, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissie ` re and Frederic Robidoux and the staff of the McGill University and Ge ́ nome Que ́ bec Innovation Centre, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. BCAC (acknowledgements by study) (ABCFS) : Maggie Angelakos, Judi Maskiell, Gillian Dite. (ABCS) C Ellen van der Schoot, Sanquin Amsterdam. (ACP) The ACP study wishes to thank the participants in the Thai Breast Cancer study. Special Thanks also go to the Thai Ministry of Public Health (MOPH), doctors and nurses who helped with the data collection process. Finally, the study would like to thank Dr Prat Boonyawongviroj, the former Permanent Secretary of MOPH and Dr Pornthep Siriwanarungsan, the Department Director-Generalof Disease Control who have supported the study throughout. (BBCS) Eileen Williams, Elaine Ryder-Mills, Kara Sargus (BIGGS) Niall McInerney, Gabrielle Colleran, Andrew Rowan, Angela Jones. (BSUCH) Peter Bugert, Medical Faculty Mannheim (CGPS) 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 (CNIO-BCS) Guillermo Pita, Charo Alonso, Daniel Herrero, Nuria A ́ lvarez, Pilar Zamora, Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO)(CTS). The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, Yani Lu, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, Eunjung Lee, and Fred Schumacher at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, and Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine. (ESTHER) Hartwig Ziegler, Sonja Wolf, Volker Hermann. (GC-HBOC) Heide Hellebrand, Stefanie Engert and GC-HBOC (Supported by Deutsche Krebshilfe). (GENICA) The GENICA Network: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tu ̈bingen, Germany [HB, Wing-Yee Lo, Christina Justenhoven], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [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 [UH], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bru ̈ning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth] (HEBCS) Kirsimari Aaltonen, Karl von Smitten, Sofia Khan, Tuomas Heikkinen, Irja Erkkila ̈ . (HMBCS) Natalia Antonenkova, Peter Hillemanns, Hans Christiansen and Johann H. Karstens (KBCP) Eija Myo ̈ ha ̈ nen, Helena Kemila ̈ inen. (kConFab/AOCS) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab 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. (LAABC) We thank all the study participants and the entire data collection team, especially Annie Fung and June Yashiki. (LMBC) Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel and Kathleen Corthouts. (MARIE) Petra Seibold, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. (MCCS) MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 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. (MBCSG) Bernard Peissel and Daniela Zaffaroni and Giulietta Scuvera of the Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; Monica Barile and Irene Feroce of the Istituto Europeo di Oncologia (IEO), Milan, Italy; and the personnel of the Cogentech Cancer Genetic Test Laboratory. (MTLGEBCS) We would like to thank Martine Tranchant (CHU de Que ́ bec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill Uni- versity) for DNA extraction, sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. (MYBRCA) Phuah Sze Yee, Peter Kang, Kang In Nee, Kavitta Sivanandan, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee, Teh Yew Ching and Nur Aishah Mohd Taib for DNA Extraction and patient recruitment. (NBHS) We thank study partcipants and research staff for their contributions and commitment to this study. (OBCS) Meeri Otsukka, Kari Mono- nen(OFBCR) Teresa Selander, Nayana Weerasooriya(ORIGO) We thank E. Krol-War- merdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. The LUMC survival data were retrieved from the Leiden hospital- based cancer registry system (ONCDOC) with the help of Dr J. Molenaar. (PBCS) Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner(pKARMA) The Swedish Medical Research Counsel. (RBCS) Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. (SASBAC) The Swedish Medical Research Counsel. (SBCGS) We thank study partcipants and research staff for their contributions and commitment to this study. (SBCS) Sue Higham, Helen Cramp, Ian Brock, Malcolm W. R. Reed, Sabapathy Balasubramanian and Dan Connley. (SEARCH) The SEARCH and EPIC teams. (SGBCC) We thank the participants and research coordinator Kimberley Chua. (SKKDKFZS) We thank all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. (TNBCC) Robert Pilarski and Charles Shapiro were instrumental in the formation of the OSU Breast Cancer Tissue Bank. We thank the Human Genetics Sample Bank for processing of samples and providing OSU Columbus area control samples. (UKBGS) We thank Breakthrough Breast Cancer 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. OCAC (acknowledgements by study) : This study would not have been possible without the contributions of the following: J Dennis, P. Hall (COGS); D. C. Tessier, F. Bacot, D. Vincent, S. LaBoissie ` re and F. Robidoux and the staff of the genotyping unit, (Genome Quebec); D. C. Whiteman, P. M. Webb, A. C. Green, N. K. Hayward, P. G. Parsons, D. M. Purdie, B. M. Smithers, D. Gotley, A. Clouston, I. Brown, S. Moore. K. Harrap, T. Sadkowski, S. O'Brien, E. Minehan, D. Roffe, S. O'Keefe, S. Lipshut, G. Connor . Berry, F. Walker, T. Barnes, J. Thomas, L. Terry, M. Connard, L. Bowes, M-R. Malt, J. White, C. Mosse, N. Tait, C. Bambach, A. Biankan, R. Brancatisano, M. Coleman, M. Cox, S. Deane, G. L. Falk, J. Gallagher, M. Hollands, T. Hugh, D. Hunt, J. Jorgensen, C. Martin, M. Richardson, G. Smith, R. Smith, D. Storey, J. Avramovic, J. Croese, J. D'Arcy, S. Fairley, J. Hansen, J. Masson, L. Nathanson, B. O'Loughlin, L. Rutherford, R. Turner, M. Windsor, J. Bessell, P. Devitt, G. Jamieson, D. Watson, S. Blamey, A. Boussioutas, R. Cade, G. Crosthwaite, I. Faragher, J. Gribbin, G. Hebbard, G. Kiroff, B. Mann, R. Millar, P. O'Brien, R. Thomas, S. Wood, S. Archer, K. Faulkner, J. Hamdorf (ACS); R. Stuart-Harris, F. Kirsten, J. Rutovitz, P. Clingan, A.Glasgow, A. Proietto, S. Braye, G. Otton, J. Shannon, T. Bonaventura, J. Stewart, S. Begbie, M. Friedlander, D. Bell, S. Baron-Hay, G. Gard, D. Nevell, N. Pavlakis, S. Valmadre, B. Young, C Camaris, R. Crouch, L. Edwards, N. Hacker, D. Marsden, G. Robertson, P. Beale, J. Beith, J. Carter, C. Dalrymple, R. Houghton, P. Russell, L. Anderson, M. Links, J. Grygiel, J. Hill, A. Brand, K. Byth, R. Jaworski, P. Harnett, R. Sharma,.G Wain, D. Purdie, D. Whiteman, B. Ward, D. Papadimos, A. Crandon, M. Cummings, K. Horwood. A. Obermair, L. Perrin, D. Wyld, J. Nicklin, M. Davy, M. K. Oehler, C. Hall, T. Dodd, T. Healy, K. Pittman, D. Henderson, J. Miller, J. Pierdes, A. Achan, P. Blomfield, D. Challis, R. McIntosh, A. Parker, B. Brown, R. Rome, D. Allen, P. Grant, S. Hyde, R. Laurie, M. Robbie, D. Healy, T. Jobling, T. Manolitsas, J. McNealage, P Rogers, B. Susil, E. Sumithran, I. Simpson, I. Haviv, K. Phillips, D. Rischin, S. Fox, D. Johnson, S. Lade, P. Waring, M. Loughrey, N.O'Callaghan, B. Murray, L. Mileshkin, P. Allan; V. Billson, J. Pyman, D. Neesham, M. Quinn, A. Hamilton, C. Underhill, R. Bell, L. F Ng, R. Blum, V.Ganju, I. Hammond, C. Stewart, Y. Leung, M. Buck, N. Zeps (ACS); G. Peuteman, T. Van Brussel and D. Smeets (BEL); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schu ̈rmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJO); G.S. Keeney, S. Windebank, C. Hilker and J. Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, 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, and WYL (NHS); L. Paddock, M. King, U. Chandran, A. Samoila, and Y. Bensman (NJO); L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia- Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (POL); ); C. Luccarini, P. Harrington the SEARCH team and ECRIC (SEA); the Scottish Gynaecological Clinical Trails group and SCOTROC1 investigators (SRO); W-H. Chow, Y-T. Gao (SWH); Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/ (TCGA); I. Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan and J. Ford (UKO); Carole Pye (UKR); a full list of the investigators who contributed to the generation of the WTCCC data is available from http://www.wtccc.org.uk/ (WTCCC). CIMBA (acknowledgements by study) : (BCFR-AU) Maggie Angelakos, Judi Maskiell, Gillian Dite, Helen Tsimiklis. (BCFR-NY) We wish to thank members and participants in the New York site of the Breast Cancer Family Registry for their contributions to the study. (BCFR-ON) We wish to thank members and participants in the Ontario Familial Breast Cancer Registry for their contributions to the study. (BFBOCC-LT) We acknowledge Vilius Rudaitis, Laimonas Gris ˇ kevic ˇ ius, Ramu ̄ nas Janavic ˇ ius (if not in the authorship). BFBOCC-LV acknowledge Drs Janis Eglitis, Anna Krilova and Aivars Stengrevics. (BMBSA) We wish to thank the families who contribute to the BMBSA study. (BRICOH) We wish to thank Yuan Chun Ding and Linda Steele for their work in participant enrolment and biospecimen and data management.(CNIO) We thank Alicia Barroso, Rosario Alonso and Guillermo Pita for their assistance. (CONSIT TEAM) Alessandra Viel and Riccardo Dolcetti of the CRO Aviano National Cancer Institute, Aviano (PN), Italy; Laura Ottini of the 'Sapienza' University, Rome, Italy; Liliana Varesco of the IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Laura Papi and Gabriele Capone of the University of Florence, Florence, Italy; Antonella Savarese and Aline Martayan of the Istituto Nazionale Tumori Regina Elena, Rome, Italy; Stefania Tommasi and Brunella Pilato of the Istituto Nazionale Tumori 'Giovanni Paolo II', Bari, Italy. (CORE) The CIMBA data management and analysis is funded through Cancer Research- UK grant C12292/A11174. ACA is a Senior Cancer Research - UK Research Fellow. (EMBRACE) RE is supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. (FCCC) We thank Ms. JoEllen Weaver and Dr Betsy Bove for their technical support. (GEMO) Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study: National Cancer Genetics Network ) UNICANCER Genetic Group * , France. We wish to thank all the GEMO collaborating groups for their contribution to this study. GEMO Collaborating Centres are: Coordinating Centres, Unite ́ Mixte de Ge ́ ne ́ tique Constitutionnelle des Cancers Fre ́ quents, Hospices Civils de Lyon - Centre Le ́ on Be ́ rard, and Equipe ) Ge ́ ne ́ tique du cancer du sein * , Centre de Recherche en Cance ́ rologie de Lyon: Olga Sinilnikova w , Sylvie Mazoyer, Francesca Damiola, Laure Barjhoux, Carole Verny-Pierre, Me ́ lanie Le ́ one, Nadia Boutry-Kryza, Alain Calender, Sophie Giraud; and Service de Ge ́ ne ́ tique Oncologique, Institut Curie, Paris: Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Etienne Rouleau, Lisa Golmard, Agne ` s Collet, Virginie Moncoutier, Ce ́ drick Lefol, Muriel Belotti, Antoine de Pauw, Camille Elan, Catherine Nogues, Emmanuelle Fourme, Anne-Marie Birot. Institut Gustave Roussy, Villejuif: Brigitte Bressac-de-Pail- lerets, Olivier Caron, Marine Guillaud-Bataille. Centre Jean Perrin, Clermont–Ferrand: Yves-Jean Bignon, Nancy Uhrhammer. Centre Le ́ on Be ́ rard, Lyon: Christine Lasset, Vale ́ rie Bonadona, Sandrine Handallou. Centre Franc ̧ ois Baclesse, Caen: Agne ` s Hardouin, Pascaline Berthet, Dominique Vaur, Laurent Castera. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Audrey Remenieras, Franc ̧ ois Eisinger. CHU Arnaud-de-Villeneuve, Montpellier: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille: Jean-Philippe Peyrat, Joe ̈ lle Fournier, Franc ̧ oise Re ́ villion, Philippe Vennin w , Claude Adenis. Centre Paul Strauss, Strasbourg: Danie ` le Muller, Jean-Pierre Fricker. Institut Bergonie ́ , Bordeaux: Emmanuelle Barouk-Simonet, Franc ̧ oise Bonnet, Virginie Bubien, Nicolas Sevenet, Michel Longy. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU Grenoble: Dominique Leroux, He ́ le ` ne Dreyfus, Christine Rebischung, Magalie Peysselon. CHU Dijon: Fanny Coron, Laurence Faivre. CHU St-Etienne: Fabienne Prieur, Marine Lebrun, Caroline Kientz. Ho ˆ tel Dieu Centre Hospitalier, Chambe ́ ry: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice: Marc Fre ́ nay. CHU Limoges: Laurence Ve ́ nat-Bouvet. CHU Nantes: Capucine Delnatte. CHU Bretonneau, Tours: Isabelle Mortemousque. Groupe Hospitalier Pitie ́ -Salpe ́ trie ` re, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les- Nancy: Johanna Sokolowska, Myriam Bronner. CHU Besanc ̧ on: Marie-Agne ` s Collonge- Rame, Alexandre Damette. Creighton University, Omaha, USA: Henry T. Lynch, Carrie L. Snyder. (G-FAST) We wish to thank the technical support of Ilse Coene en Brecht Crombez. (HCSC) We acknowledge Alicia Tosar for her technical assistance(HEBCS) HEBCS would like to thank Dr Kristiina Aittoma ̈ ki, Taru A. Muranen, Drs Carl Blomqvist and Kirsimari Aaltonen and RNs Irja Erkkila ̈ and Virpi Palola for their help with the HEBCS data and samples. (HEBON) The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centres: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, J.L. de Lange, R. Wijnands; Erasmus Medical Center, Rotterdam, NL: J.M. Colle ́ e, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, 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, R.B. van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M. Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, NL: E.B. Go ́ mez- Garcia, M.J. Blok; University Medical Center Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer Organization (IKNL): S. Siesling, J.Verloop; The Dutch Pathology Registry (PALGA): L.I.H. Overbeek. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scien- tific 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. HEBON thanks the registration teams of IKNL and PALGA for part of the data collection. (HRBCP) We wish to thank Hong Kong Sanatoriuma and Hospital for their continual support. (HUNBOCS) We wish to thank the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Tibor Vaszko, Aniko Bozsik, Timea Pocza, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clin- icians and patients for their contributions to this study.(HVH) We wish to thank the Oncogenetics Group (VHIO), and the High Risk and Cancer Prevention Unit of the University Hospital Vall d'Hebron.(ICO) We wish to thank the ICO Hereditary Cancer Program team led by Dr Gabriel Capella. (INHERIT) We would like to thank Dr Martine Dumont, Martine Tranchant for sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. J.S. and P.S. were part of the QC and Genotyping coordinating group of iCOGS (BCAC and CIMBA). (IPOBCS) We wish to thank Drs Ana Peixoto, Catarina Santos, Patrı ́ cia Rocha and Pedro Pinto for their skilful contribution to the study. (KCONFAB) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab 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. (MODSQUAD) Modifier Study of Quantitative Effects on Disease (MODSQUAD): we acknowledge ModSQuaD members Csilla Szabo (National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA); Lenka Foretova and Eva Machackova (Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic); and Michal Zikan, Petr Pohlreich and Zdenek Kleibl (Oncogynecologic Center and Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic). (MSKCC) Anne Lincoln, Lauren Jacobs. (NICCC) We wish to thank the NICCC National Familial Cancer Consultation Service team led by Sara Dishon, the lab team led by Dr Flavio Lejbkowicz, and the research field operations team led by Dr Mila Pinchev. (NRG Oncology) We thank the investigators of the Australia New Zealand NRG Oncology group. (OCGN) We wish to thank members and participants in the Ontario Cancer Genetics Network for their contributions to the study. (OSU CCG) Leigha Senter, Kevin Sweet, Caroline Craven, and Michelle O'Conor were instrumental in accrual of study participants, ascertainment of medical records and database management. Samples were processed by the OSU Human Genetics Sample Bank. (SEABASS) We would like to thank Yip Cheng Har, Nur Aishah Mohd Taib, Phuah Sze Yee, Norhashimah Hassan and all the research nurses, research assistants and doctors involved in the MyBrCa Study for assistance in patient recruitment, data collection and sample preparation. In addition, we thank Philip Iau, Sng Jen-Hwei and Sharifah Nor Akmal for contributing samples from the Singapore Breast Cancer Study nd the HUKM-HKL Study respectively. The Malaysian Breast Cancer Genetic Study is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HIR/MOHE/06) and charitable funding from Cancer Research Initiatives Foundation. (SMC) SMC team wishes to acknowledge the assistance of the Meirav Comprehensice breast cancer center team at the Sheba Medical Center for assistance in this study. (SWE-BRCA) Swedish scientists participating as SWE-BRCA collaborators are: from Lund University and University Hospital: Åke Borg, Håkan Olsson, Helena Jernstro ̈ m, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna O ̈ fverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza, Johanna Rantala; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellstro ̈ m Pigg, Richard Rosenquist; from Linko ̈ ping University Hospital: Marie Stenmark-Askmalm, Sigrun Lied- gren(UCHICAGO) We wish to thank Cecilia Zvocec, Qun Niu, physicians, genetic counsellors, research nurses and staff of the Cancer Risk Clinic for their contributions to this resource, and the many families who contribute to our programme. (UCLA) We thank Joyce Seldon MSGC and Lorna Kwan, MPH for assembling the data for this study. (UCSF) We would like to thank Dr Robert Nussbaum and the following genetic coun- sellors for participant recruitment: Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad. And thanks to Ms. Salina Chan for her data management. (UKFOCR) We thank Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. (VFCTG) Geoffrey Lindeman, Marion Harris, Martin Delatycki of the Victorian Familial Cancer Trials Group. We thank Sarah Sawyer and Rebecca Driessen for assembling this data and Ella Thompson for performing all DNA amplification. Grant Support : The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175—HEALTH-F2-2009- 223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community ́ s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The CIMBA data management and analytical work is funded by Cancer Research UK (C12292/A11174, C12292/A20861). 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, 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, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The Ovarian Cancer Association Consortium 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. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute. Personal support: K.L. is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). This project was supported in part by a Program Project Development Grant from the Ovarian Cancer Research Fund (S.A.G and A.M). The in vitro aspects of this project were performed within the Norris Cancer Centre at USC, which is supported in part by award number P30CA014089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. D.F.E. is a Principal Research Fellow of Cancer Research UK. A.C.A. is a Cancer Research—UK Senior Cancer Research Fellow. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. (WCP) B.Y.K 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. L.E.K. is supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). S.P.K. is supported by a Gates Cambridge Scholarship. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. RB was a Cancer Institute NSW Clinical Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. A.K.G. was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. S.L.E. and J.D.F. are supported by Fellowships from the National Breast Cancer Foundation (NBCF) Australia and NHMRC project grant (1058415). Funding : BCAC: 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 centres 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. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The ACP study is funded by the Breast Cancer Research Trust, UK. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN).ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre.The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev HospitalThe CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tema ́ tica de Investigacio ́ n Cooperativa en Ca ́ ncer and grants from the Asociacio ́ n Espan ̃ ola Contra el Ca ́ ncer and the Fondo de Investigacio ́ n Sanitario (PI11/00923 and PI12/00070). 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 cur- rently funded through the National Institutes of Health (R01 CA77398). 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. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Wu ̈rttemberg 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). The GC-HBOC was supported by Deutsche Krebshilfe (107 352). 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 HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. 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. 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). 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. LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII.The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419], 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 '5x1000'). 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 Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19/550), Singapore and the National medical Research Council, Singa- pore (NMRC/CG/SERI/2010). 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 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 Ontario Familial Breast Cancer Registry (OFBCR) 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 centres 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 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. The pKARMA study was supported by Ma ̈ rit and Hans Rausings Initiative Against Breast CancerThe RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was sup- ported 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, 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 Yorkshire Cancer Research S295, S299, S305PA and Sheffield Experimental Cancer Medicine Centre.SEARCH is funded by a programme grant from Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.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.SKKDKFZS is supported by the DKFZ. 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 Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, 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) - ARISTEIA. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. Funding : OCAC : Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389 V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L and S Milken Foun- dation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50- CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01- CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01- CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01- CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01- CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01- CA071966, R01-CA063678 and Intramural research funds); the US Army Medical Research and Material Command (DAMD17-98-1- 8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1- 0669, W81XWH-10-1-0280); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wu ̈rttemberg through Medical Faculty of the University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital 'Womens Health Theme' and the Royal Marsden Hospital; WorkSafeBC. Funding : CIMBA (BCFR—all) : 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 centres 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-LT) BFBOCC is partly supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; (BIDMC) BIDMC is supported by the Breast Cancer Research Foundation. (BMBSA) BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. (BRICOH) SLN was partially supported by the Morris and Horowitz Familes Endowed Professorship. (CBCS) This work was supported by the NEYE Foundation. (CNIO) This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilen ̃ a Foundation (FMMA) and SAF2010-20493 (COH-CCGCRN) City of Hope Clinical Cancer Genetics Community 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 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) 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') to Siranoush Manoukian. (CORE) The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A11174 and C1287/A10118.SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer Research -UK Senior Cancer Research Fellow. (DEMOKRITOS) 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 Frame- work (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA. Investing in knowledge society through the European Social Fund.(DKFZ) The DKFZ study was supported by the DKFZ. (EMBRACE) EMBRACE is supported by 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. (FCCC) The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. (GC-HBOC) The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). (GEMO) The study was supported by the 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). (GEORGETOWN) CI received support from the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial Cancer Research, and Swing Fore the Cure. (G-FAST) Kim De Leeneer is supported by GOA grant BOF10/ GOA/019 (Ghent University) and spearhead financing of Ghent University Hospital. (HCSC) HCSC supported by a grant RD12/0036/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. (HEBCS) The HEBCS was financially supported by the Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. (HEBON) The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection. (HRBCP) HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong (HUNBOCS) Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, OTKA K-112228 and the Norwegian EEA Financial Mechanism Hu0115/NA/2008-3/OP-9. (ICO) Contract grant sponsor: Asociacio ́ n Espan ̃ ola Contra el Ca ́ ncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/ 00748, PI13/00285, PIE13/00022, 2009SGR290 and 2014SGR364. (IHCC) The IHCC was supported by Grant PBZ_KBN_122/P05/2004(ILUH) The ILUH group was supported by the Icelandic Association 'Walking for Breast Cancer Research' and by the Landspitali University Hospital Research Fund. (INHERIT) This work was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI- 701. (IOVHBOCS) IOVHBOCS is supported by Ministero della Salute and '5 1,000' Istituto Oncologico Veneto grant. (IPOBCS) This study was in part supported by Liga Portuguesa Contra o Cancro.(KCONFAB) 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; (KOHBRA) KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs,Republic of Korea (1020350). (MAYO) MAYO is supported by NIH grants CA116167, CA128978 and CA176785, 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), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. (MCGILL) Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade (MODSQUAD) MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) 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) MSKCC is supported by grants from the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin Research Fund. (NAROD) 1R01 CA149429- 01. (NCI) The research of Drs MH Greene, JT Loud and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. (NICCC) NICCC is supported by Clalit Health Services in Israel. Some of it's activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. (NNPIO) This work has been supported by the Russian Federation for Basic Research (grants 13-04-92613, 14-04-93959 and 15-04-01744). (NRG Oncology) This study was supported by National Cancer Institute grants to the NRG Oncology Administrative Office and Tissue Bank (CA 27469), the NRG Oncology Statistical and Data Center (CA 37517), and NRG Oncology's Cancer Prevention and Control Committee (CA 101165). (OSU CCG) OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. (PBCS) This work was supported by the ITT (Istituto Toscano Tumori) grants 2011-2013. (SEABASS) Ministry of Science, Technol- ogy and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. (SMC) This project was partially funded through a grant by the Isreal cancer association and the funding for the Israeli Inherited breast cancer consortium (SWE-BRCA) SWE-BRCA collaborators are supported by the Swedish Cancer Society. (UCHICAGO) UCHICAGO is supported by 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. OIO is an ACS Clinical Research Professor.(UCLA) Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. (UCSF) UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. (UKFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. (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) Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program;Hackers for Hope Pittsburgh. (VFCTG) Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation unding 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, 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, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund and grants R01-CA122443 and P50-CA136393. ; Sí

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