Suchergebnisse

Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM 2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM 2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 μg/m 3 in PM 2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 μg/m 3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM 2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 μg/m 3 an increase of 5 μg/m 3 in PM 2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

OBJECTIVE To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN Pooled analysis of eight cohorts. SETTING Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES Deaths due to natural causes and cause specific mortality. RESULTS Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 mu g/m(3) in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 mu g/m(3) increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 mu g/m(3) an increase of 5 mu g/m(3) in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM(2.5)), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM(2.5), nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m(3) in PM(2.5) was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m(3) increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM(2.5), nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m(3) an increase of 5 µg/m(3) in PM(2.5) was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk. ; This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Please see the Supplemental Information section for a detailed listing of study-specific funding. Co-authors Xiaoqin Xiong (Information Management Systems, Inc.), Dennis Maeder (Leidos Biomedical Research, Inc.) and Michelle Brotzman (Westat) are employed by commercial enterprises, and received salary from these companies to support this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Sí

International audience ; Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM 2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM 2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 μg/m 3 in PM 2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 μg/m 3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM 2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 μg/m 3 an increase of 5 μg/m 3 in PM 2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

International audience ; Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM 2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM 2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 μg/m 3 in PM 2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 μg/m 3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM 2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 μg/m 3 an increase of 5 μg/m 3 in PM 2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

International audience ; Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM 2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM 2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 μg/m 3 in PM 2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 μg/m 3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM 2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 μg/m 3 an increase of 5 μg/m 3 in PM 2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

International audience ; Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM 2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM 2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 μg/m 3 in PM 2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 μg/m 3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM 2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 μg/m 3 an increase of 5 μg/m 3 in PM 2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

International audience ; Objective To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. Design Pooled analysis of eight cohorts. Setting Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. Participants 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM 2.5), nitrogen dioxide, ozone, and black carbon. Main outcome measures Deaths due to natural causes and cause specific mortality. Results Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM 2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 μg/m 3 in PM 2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 μg/m 3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM 2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 μg/m 3 an increase of 5 μg/m 3 in PM 2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. Conclusions Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease. ; The ENGAGE Project was funded under the European Union Framework 7 – Health Theme (HEALTH-F4-2007- 201413). The InterAct project received funding from the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community). The EPIC-CVD study was supported by core funding from the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), and the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. C.P.N is funded by the BHF. V.C., C.P.N. and N.J.S. are supported by the NIHR Leicester Cardiovascular Biomedical Research Centre and N.J.S. holds an NIHR Senior Investigator award. Chen Li is support by a 4-year Wellcome Trust PhD Studentship; CL, LAL, NJW are funded by the Medical Research Council (MC_UU_12015/1). NJW is an NIHR Senior Investigator. JD is funded by the National Institute for Health Research [Senior Investigator Award]. Cohort specific and further acknowledgements are given in the Supplemental Data.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene. ; This work was supported by RO1 CA154823, the Lustgarten Foundation, and federal funds from the NCI, US NIH under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Geno-typing Services were provided by the CIDR and the NCIs CGR. CIDR is fully funded through a federal contract from the NIH to the Johns Hopkins University, contract number HHSN268201100011I. The IARC/Central Europe study was supported by a grant from the US NCI at the NIH (R03 CA123546-02) and grants from the Ministry of Health of the Czech Republic (NR 9029-4/2006, NR9422-3, NR9998-3, and MH CZ- DRO-MMCI 00209805). The work at Johns Hopkins University was supported by the NCI Grants P50CA062924 and R01CA97075. Additional support was provided by, Susan Wojcicki, and Dennis Troper, and the Sol Goldman Pancreas Cancer Research Center. The Mayo Clinic Biospecimen Resource for Pancreas Research study is supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701). The Memorial Sloan Ket- tering Cancer Center Pancreatic Tumor Registry is supported by P30CA008748, the Geoffrey Beene Foundation, the Arnold and Arlene Goldstein Family, Foundation, and the Society of MSKCC. The PACIFIC Study was supported by RO1CA102765, Kaiser Permanente, and Group Health Cooperative. The Queensland Pancreatic Cancer Study was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC; Grant number 442302). R.E.N. is supported by a NHMRC Senior Research Fellowship (#1060183). The UCSF pancreas study was supported by NIH-NCI grants (R01CA1009767, R01CA109767-S1, and R0CA059706) and the Joan Rombauer Pancreatic Cancer Fund. Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting pro- gram; the NCIs SEER Program under contract HSN261201000140C awarded to CPIC; and the CDCs National Program of Cancer Registries, under agreement #U58DP003862-01 awarded to the California Department of Public Health. The Yale (CT) pancreas cancer study is supported by NCI at the U.S. NIH, grant 5R01CA098870. The cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access is gratefully acknowledged. The Connecticut Pancreas Cancer Study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in that study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The authors assume full responsibility for analyses and interpretation of these data. Studies included in PAN- DoRA were partly funded by the Czech Science Foundation (No. P301/12/1734), the Internal Grant Agency of the Czech Ministry of Health (IGA NT 13 263); the Baden- Württemberg State Ministry of Research, Science and Arts (Professor H. Brenner), the Heidelberger EPZ-Pancobank (Professor M.W. Büchler and team: Professor T. Hackert, Dr. N. A. Giese, Dr. Ch. Tjaden, E. Soyka, M. Meinhardt; Heidelberger. Stiftung Chir- urgie and BMBF grant 01GS08114), the BMBH (Professor P. Schirmacher; BMBF grant 01EY1101), the " 5 × 1000 " voluntary contribution of the Italian Government, the Italian Ministry of Health (RC1203GA57, RC1303GA53, RC1303GA54, and RC1303GA50), the Italian Association for Research on Cancer (Professor A. Scarpa; AIRC n. 12182), the Italian Ministry of Research (Professor A. Scarpa; FIRB - RBAP10AHJB), the Italian FIMP-Ministry of Health (Professor A. Scarpa; 12 CUP_J33G13000210001), and by the National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, UK. We would like to acknowledge the contribution of Dr. Frederike Dijk and Professor Oliver Busch (Academic Medical Center, Amsterdam, the Netherlands). Assistance with genotype data quality control was provided by Cecelia Laurie and Cathy Laurie at the University of Washington Genetic Analysis Center. The American Cancer Society (ACS) funds the creation, maintenance, and updating of the Cancer Prevention Study II cohort. Cancer incidence data for CLUE were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, 201 W. Preston Street, Room 400, Baltimore, MD 21201, http://phpa.dhmh.maryland.gov/ cancer , 410-767-4055. We acknowledge the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention for the funds that support the collection and availability of the cancer registry data. We thank all the CLUE participants. The Melbourne Col- laborative Cohort Study (MCCS) recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057 and 396414 and by the 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 NYU study (AZJ and AAA) was funded by NIH R01 CA098661, UM1 CA182934 and center grants P30 CA016087 and P30 ES000260. The PANKRAS II Study in Spain was supported by research grants from Instituto de Salud Carlos III-FEDER, Spain: Fondo de Investigaciones Sanitarias (FIS; #PI13/00082 and #PI15/01573) and Red Temática de Investigación Cooperativa en Cáncer, Spain (#RD12/ 0036/0050); and European Cooperation in Science and Technology (COST Action #BM1204: EU_Pancreas), Ministerio de Ciencia y Tecnología (CICYT SAF 2000-0097), Fondo de Investigación Sanitaria (95/0017), Madrid, Spain; Generalitat de Catalunya(CIRIT—SGR);"Red temática de investigación cooperativa de centros en Cáncer (C03/10),"Red temática de investigación cooperativa de centros en Epidemiología y salud pública(C03/09), and CIBER de Epidemiología (CIBERESP), Madrid. The Physicians 'Health Study was supported by research grants CA-097193, CA-34944, CA-40360, HL- 26490, and HL-34595 from the NIH, Bethesda, MD, USA. The Womens Health Study was supported by research grants CA-047988, HL-043851, HL-080467, and HL-099355 from the NIH, Bethesda, MD, USA. Health Professionals Follow-up Study is supported by NIH grant UM1 CA167552 from the NCI, Bethesda, MD, USA. Nurses ' Health Study is supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449 from the NCI, Bethesda, MD, USA. Additional support from the Hale Center for Pancreatic Cancer Research, U01 CA21017 from the NCI, Bethesda, MD, USA, and the United States Department of Defense CA130288, Lustgarten Foundation, Pancreatic Cancer Action Network, Noble Effort Fund, Peter R. Leavitt Family Fund, Wexler Family Fund, and Promises for Purple to B.M. Wolpin is acknowledged. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf . We thank Laurie Burdett, Aurelie Vogt, BelyndaHicks, Amy Hutchinson, Meredith Yeager, and other staff at the NCI's Division ofEpidemiology and Genetics (DECG) CGR for GWAS genotyping. We also thank Bao Tran, Jyoti Shetty, and other members of the NCI Center for Cancer Research (CCR) Sequencing Facility for sequencing RNA from histologically normal pancreatic tissue samples (LTG samples). This study utilized the high-performance computational cap- abilities of the Biowulf Linux cluster at the NIH, Bethesda, MD, USA (http://biowulf.nih.gov). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the NIH, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the pancreatic tissue data from the GTEx Portal on 05/04/17. The results published here are in part based upon data generated by The Cancer Genome Atlas (TCGA) managed by the NCI and NHGRI. Information about TCGA can be found at http://cancergenome.nih.gov/. We acknowledge the clinical contributors that provided PDAC samples and the data producers of RNA-seq and GWAS genotype data from TCGA Research Network. The data set used for the analyses described in this manuscript was obtained by formal permission through the TCGA Data Access Committee (DAC) ; Sí