Journal article

Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Evelina Mocci, Prosenjit Kundu, William Wheeler, Alan A Arslan, Laura E Beane-Freeman, Paige M Bracci, Paul Brennan, Federico Canzian, Mengmeng Du, Steven Gallinger, Graham G Giles, Phyllis J Goodman, Charles Kooperberg, Loic Le Marchand, Rachel E Neale, Xiao-Ou Shu, Kala Visvanathan, Emily White, Wei Zheng, Demetrius Albanes Show all

CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2021

Abstract

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative intera..

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Grants

Awarded by Patient-Centered Outcomes Research Institute Award


Awarded by U.S. NCI at the NIH


Awarded by Ministry of Health of the Czech Republic


Awarded by NCI


Awarded by NCI, U.S. NIH


Awarded by Mayo Clinic SPORE in Pancreatic Cancer


Awarded by Kaiser Permanente and Group Health Cooperative


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by NIH-NCI grants


Awarded by NCI's SEER Program


Awarded by CDC's National Program of Cancer Registries


Awarded by NCI at the U.S. NIH


Awarded by Czech Science Foundation


Awarded by Internal Grant Agency of the Czech Ministry of Health


Awarded by Heidelberger EPZ-Pancobank (Heidelberger Stiftung Chirurgie and BMBF)


Awarded by BMBH


Awarded by Italian Ministry of Health


Awarded by Italian Association for Research on Cancer (AIRC)


Awarded by Italian Ministry of Research


Awarded by Italian FIMP-Ministry of Health


Awarded by Australian National Health and Medical Research Council


Awarded by NIH


Awarded by Instituto de Salud Carlos III-FEDER, Spain: Fondo de Investigaciones Sanitarias (FIS)


Awarded by Red Tematica de Investigacion Cooperativa en Cancer, Spain


Awarded by European Cooperation in Science and Technology (COST Action)


Awarded by Ministerio de Ciencia y Tecnologia


Awarded by Fondo de Investigacion Sanitaria, Madrid, Spain


Awarded by Red tematica de investigacion cooperativa de centros en Cancer


Awarded by Red tematica de investigacion cooperativa de centros en Epidemiologia y salud Publica


Awarded by National Institutes of Health, Bethesda, MD


Awarded by NIH from the NCI, Bethesda, MD


Awarded by NCI, Bethesda, MD


Awarded by United States Department of Defense


Awarded by National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services


Awarded by NHMRC Senior Research Fellowship



Funding Acknowledgements

This work was supported by RO1CA154823 and P50CA062924 (to principal investigator A.P. Klein), R01 HG010480-01 (to principal investigator N. Chatterjee), Patient-Centered Outcomes Research Institute Award (ME-1602-34530), and the Intramural Research Program, Division of Cancer Epidemiology and Genetics, NCI (to principal investigator R. Stolzenberg-Solomon). Funding for the parent studies are listed below.The IARC/Central Europe study was supported by a grant from the U.S. 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, MH CZ-DRO-MMCI 00209805).The work at Johns Hopkins University (Baltimore, MD) was supported by the NCI grants P50CA062924 and R01CA97075. Additional support was provided by the Lustgarten Foundation, Susan Wojcicki and Dennis Troper, and the Sol Goldman Pancreas Cancer Research Center. This work was supported by RO1 CA154823 and federal funds from the NCI, U.S. NIH under contract number HHSN261200800001E.The Mayo Clinic Biospecimen Resource for Pancreas Research study is supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701).The Memorial Sloan Kettering 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. We acknowledge the contribution of Irene Orlow, MS, PhD to this analysis.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. Neale 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 program; the NCI's SEER Program under contract HSN261201000140C awarded to CPIC; and the CDC's 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 PANDoRA 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-W_urttemberg State Ministry of Research, Science and Arts (H. Brenner), the Heidelberger EPZ-Pancobank (M.W. B_uchler and team: T. Hackert, N.A. Giese, Ch. Tjaden, E. Soyka, M. Meinhardt; Heidelberger Stiftung Chirurgie and BMBF grant 01GS08114), the BMBH (P. Schirmacher; BMBF grant 01EY1101), the "5x1000" voluntary contribution of the Italian Government, the Italian Ministry of Health (RC1203GA57, RC1303GA53, RC1303GA54, RC1303GA50), the Italian Association for Research on Cancer (A. Scarpa; AIRC n. 12182), the Italian Ministry of Research (A. Scarpa; FIRB -RBAP10AHJB), the Italian FIMP-Ministry of Health (A. Scarpa; 12 CUP_J33G13000210001), and by the National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, UK. The authors would like to acknowledge the contribution of Frederike Dijk and Oliver Busch (Academic Medical Center, Amsterdam, the Netherlands).Assistance with genotype data quality control was provided by Cecelia Laurie and Cathy Laurie at 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, MD21201, http://phpa.dhmh.maryland.gov/cancer, 410-767-4055.The authors 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. They thank all the CLUE participants.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.TheNYUstudy (A. Zeleniuch-Jacquotte and A.A. Arslan) 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 Tem~atica de Investigaci~on Cooperativa en C~ancer, Spain (#RD12/0036/0050); and European Cooperation in Science and Technology (COST Action #BM1204: EU_Pancreas), Ministerio de Ciencia y Tecnologia (CICYT SAF 2000-0097), Fondo de Investigaci~on Sanitaria (95/0017), Madrid, Spain; Generalitat de Catalunya (CIRIT -SGR); "Red tematica de investigacion cooperativa de centros en C~ancer" (C03/10), "Red tematica de investigacion cooperativa de centros en Epidemiologia y salud Publica" (C03/09), and CIBER de Epidemiologia (CIBERESP), Madrid.The Physicians' Health Study was supported by research grants CA-097193, CA34944, CA-40360, HL-26490, and HL-34595 from the NIH, Bethesda, MD.The Women's Health Study was supported by research grants CA182913, CA047988, HL-043851, HL-080467, and HL-099355 from the National Institutes of Health, Bethesda, MD.Health Professionals Follow-up Study is supported by NIH grantUM1CA167552. from the NCI, Bethesda, MD.Nurses' Health Study is supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449 from the NCI, Bethesda, MD.Additional support from the Hale Center for Pancreatic Cancer Research, U01 CA21017 from theNCI, Bethesda, MD, 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.The Shanghai Men's Health Study is supported by NIH grantUM1CA173640. The Shanghai Women's Health Study is supported by NIH grant UM1CA182910.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.SELECT study is supported by NIH grant award number U10 CA37429 (C.D. Blanke), and UM1 CA182883 (C.M. Tangen/I.M. Thompson). The authors thank the site investigators and staff and, most importantly, the participants from PCPT and SELECT who donated their time to this trial.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 article were obtained from the tissue data from the GTEx Portal on June 2019 and July 2020.