Journal article

Genome-Wide Gene-Diabetes and Gene-Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia

Hongwei Tang, Lai Jiang, Rachael Z Stolzenberg-Solomon, 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 EPIDEMIOLOGY BIOMARKERS & PREVENTION | AMER ASSOC CANCER RESEARCH | Published : 2020

Abstract

BACKGROUND: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. METHODS: We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m2) and diabetes (duration ≥3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency ≥0.005, g..

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Grants

Awarded by NIH


Awarded by Ministry of Health of the Czech Republic


Awarded by NCI grants


Awarded by NCI


Awarded by Mayo Clinic SPORE in Pancreatic Cancer


Awarded by Khalifa Bin Zayed Al Nahyan Foundation


Awarded by NCI grant


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


Awarded by NHMRC Senior Research Fellowship


Awarded by NIH-NCI


Awarded by State of Connecticut Department of Public Health Human Investigation Committee - Czech Science Foundation


Awarded by Internal Grant Agency of the Czech Ministry of Health


Awarded by BMBF


Awarded by Italian Ministry of Health


Awarded by AIRC


Awarded by Italian Ministry of Research


Awarded by Italian FIMP-Ministry of Health


Awarded by Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene (Baltimore)


Awarded by National Program of Cancer Registries of the Centers for Disease Control and Prevention - VicHealth and Cancer Council Victoria


Awarded by Australian Institute of Health and Welfare - NIH


Awarded by 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 Generalitat de Catalunya


Awarded by CIBER de Epidemiologia (CIBERESP), Madrid, Spain


Awarded by Hale Center for Pancreatic Cancer Research


Awarded by United States Department of Defense


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


Funding Acknowledgements

This work was supported by the NIH grants R01CA169122 (to P. Wei) and UH2CA191284 (to P. Kraft). The IARC/Central Europe study was supported by NIH grant 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 the Lustgarten Foundation, and Susan Wojcicki and Dennis Troper and the Sol Goldman Pancreas Cancer Research Center. This work was supported by an NCI grant R01 CA154823. The Mayo Clinic Biospecimen Resource for Pancreas Research study is supported by the Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701). The MD Anderson Cancer Center study was supported by the NIH grant R01CA98030 and a grant from the Khalifa Bin Zayed Al Nahyan Foundation. The Memorial Sloan Kettering Cancer Center Pancreatic Tumor Registry was 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 the NCI grant R01CA102765, and 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 was supported by an NHMRC Senior Research Fellowship (#1060183). The UCSF pancreas study was supported by NIH-NCI grants (R01CA1009767, R01CA109767S1, and R0CA059706) and the Joan Rombauer Pancreatic Cancer Fund. The Yale (CT) pancreas cancer study was supported by the NCI 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. 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 (to Prof. H. Brenner), the Heidelberger EPZ-Pancobank (to Prof. M.W. Buchler and team: Prof. T. Hackert, Dr. N. A. Giese, Dr. Ch. Tjaden, E. Soyka, andM. Meinhardt; Heidelberger Stiftung Chirurgie and BMBF grant 01GS08114), the BMBH (to Prof. P. Schirmacher; BMBF grant 01EY1101), the "5 x 1000" voluntary contribution of the Italian Government, the Italian Ministry of Health (RC1203GA57, RC1303GA53, RC1303GA54, and RC1303GA50), the Italian Association for Research on Cancer (to Prof. A. Scarpa; AIRC n. 12182), the Italian Ministry of Research (to Prof. A. Scarpa; FIRB -RBAP10AHJB), the Italian FIMP-Ministry of Health (to Prof. A. Scarpa; 12 CUP_J33G13000210001), and by the National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, United Kingdom. We would like to acknowledge the contribution of Dr Frederike Dijk and Prof. Oliver Busch (Academic Medical Center, Amsterdam, the Netherlands). The American Cancer Society 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 (Baltimore, MD; http://phpa.dhmh.maryland.gov/cancer, 410-767-4055).Weacknowledge 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 Collaborative Cohort Study (MCCS) recruitment was funded by VicHealth and Cancer Council Victoria. TheMCCSwas further supported by AustralianNHMRCgrants 209057 and 396414 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 NYU study (to 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 Tematica de Investigacion Cooperativa en Cancer, Spain (#RD12/0036/0050); 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); and "Red tematica de investigacion cooperativa de centros en Cancer" (C03/10), "Red tematica de investigacion cooperativa de centros en Epidemiologia y salud publica" (C03/09), and CIBER de Epidemiologia (CIBERESP), Madrid, Spain. 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). The Women's Health Study was supported by research grants CA-047988, HL-043851, HL-080467, and HL-099355 from the NIH (Bethesda, MD). Health Professionals Follow-up Study was supported by NIH grant UM1 CA167552 from the NCI (Bethesda, MD). Nurses' Health Study was supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449 from the NCI (Bethesda, MD). Additional support was provided from the Hale Center for Pancreatic Cancer Research, U01 CA21017 from the NCI (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 WHI program was 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%20 Investigator%20Long%20List.pdf.