Journal article

Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk

Xiaoliang Wang, Yu-Ru Su, Paneen S Petersen, Stephanie Bien, Stephanie L Schmit, David A Drew, Demetrius Albanes, Sonja Berndt, Hermann Brenner, Peter T Campbell, Graham Casey, Jenny Cheng-Claude, Steven Gallinger, Stephen B Gruber, Robert W Haile, Tabitha A Harrison, Michael Hoffmeister, Eric J Jacobs, Mark A Jenkins, Amit D Joshi Show all

Cancer Epidemiology Biomarkers & Prevention | AMER ASSOC CANCER RESEARCH | Published : 2020

Abstract

BACKGROUND: Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk. METHODS: Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed S..

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Grants

Awarded by Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): NCI, NIH, U.S. Department of Health and Human Services


Awarded by NIH/NCI Cancer Center


Awarded by National Institutes of Health to The Johns Hopkins University


Awarded by Intramural Research Program of the NCI, NIH, and by U.S. Public Health Service - NCI, Department of Health and Human Services


Awarded by NCI, NIH


Awarded by Colon CFR centers: Australasian Colorectal Cancer Family Registry (NCI/NIH)


Awarded by USC Consortium Colorectal Cancer Family Registry (NCI/NIH)


Awarded by Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH)


Awarded by Ontario Familial Colorectal Cancer Registry (NCI/NIH)


Awarded by Seattle Colorectal Cancer Family Registry (NCI/NIH)


Awarded by University of Hawaii Colorectal Cancer Family Registry (NCI/NIH)


Awarded by National Cancer Institute to Fred Hutchinson Cancer Research Center


Awarded by Hawai'i Department of Health


Awarded by California Department of Public Health


Awarded by (NCI/NIH), U.S. Department of Health and Human Services


Awarded by National Institutes of Environmental Health Sciences, NIH


Awarded by FEDER


Awarded by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government


Awarded by Junta de Castilla y Leon


Awarded by Plataforma Biobancos


Awarded by German Research Council


Awarded by German Federal Ministry of Education and Research


Awarded by NIH


Awarded by Damon Runyon Cancer Research Foundation


Awarded by Australian NHMRC


Awarded by Ontario Registry for Studies of Familial Colorectal Cancer


Awarded by NIH, U.S. Department of Health and Human Services



Funding Acknowledgements

CPS-II: The authors thank the CPS-II participants and StudyManagement Group for their invaluable contributions to this research. The authors 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, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program.Ontario Institute for Cancer Research, through generous support from theOntario Ministry of Research and Innovation NFCCR: The authors acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Genome Quebec Innovation Centre, Montreal, Canada, for genotyping the Sequenom panel in the NFCCR samples. Funding was provided to M.O. Woods by the Canadian Cancer Society Research Institute.Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.PLCO: This study is supported by Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH. The authors thank the PLCO Cancer Screening Trial screening center investigators and the staff from Information Management Services Inc and Westat Inc. Most importantly, the authors thank the study participants for their contributions that made this study possible.Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): NCI, NIH, U.S. Department of Health and Human Services (U01 CA137088, R01 CA059045, R01201407). This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268201200008I.ATBC: The ATBC Study is supported by the Intramural Research Program of the NCI, NIH, and by U.S. Public Health Service contract HHSN261201500005C from the NCI, Department of Health and Human Services.COLO2&3: NIH (R01 CA60987).The Colon Cancer Family Registry (CFR) Illumina GWAS was supported by funding from the NCI, NIH (grant numbers U01 CA122839, R01 CA143247). The Colon CFR/CORECT Affymetrix Axiom GWAS and OncoArray GWAS were supported by funding from NCI, NIH (grant number U19 CA148107, to S.B. Gruber). The Colon CFR participant recruitment and collection of data and biospecimens used in this study were supported by the NCI, NIH (grant number U01 CA167551) and through cooperative agreements with the following Colon CFR centers: Australasian Colorectal Cancer Family Registry (NCI/NIH grant numbers U01 CA074778 and U01/U24 CA097735, to M.A. Jenkins), USC Consortium Colorectal Cancer Family Registry (NCI/NIH grant numbers U01/U24 CA074799, to R.W. Haile), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH grant number U01/U24 CA074800, to N.M. Lindor), Ontario Familial Colorectal Cancer Registry (NCI/NIH grant number U01/U24 CA074783, to S.J. Gallinger), Seattle Colorectal Cancer Family Registry (NCI/NIH grant number U01/U24 CA074794, to P.A. Newcomb), and University of Hawaii Colorectal Cancer Family Registry (NCI/NIH grant number U01/U24 CA074806, to L. Le Marchand). Additional support for case ascertainment was provided from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute to Fred Hutchinson Cancer Research Center (control nos. N01-CN-67009 and N01-PC-35142; contract no. HHSN2612013000121), the Hawai'i Department of Health (control nos. N01-PC-67001 and N01-PC-35137; contract no. HHSN26120100037C), and the California Department of Public Health (contracts HHSN261201000035C awarded to the University of Southern California, and the following state cancer registries: AZ, CO, MN, NC, NH, and by the Victoria Cancer Registry and Ontario Cancer Registry).Colorectal Cancer Transdisciplinary (CORECT) Study: The CORECT Study was supported by the (NCI/NIH), U.S. Department of Health and Human Services (grant numbers U19 CA148107, R01 CA81488, P30 CA014089, R01 CA197350; P01 CA196569; R01 CA201407) and National Institutes of Environmental Health Sciences, NIH (grant number T32 ES013678).CPS-II: The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. This study was conducted with Institutional Review Board approval.CRCGEN: Colorectal Cancer Genetics & Genomics, Spanish study was supported by Instituto de Salud Carlos III, cofunded by FEDER funds -a way to build Europe(grant numbers PI14-613 and PI09-1286), Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (grant number 2017SGR723), and Junta de Castilla y Leon (grant number LE22A10-2). Sample collection of this work was supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC), Plataforma Biobancos PT13/0010/0013 and ICOBIOBANC, sponsored by the Catalan Institute of Oncology.DACHS: This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH117/1-1, HO5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1, and BR 1704/17-1); the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany; and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A, and 01ER1505B).DALS: NIH (grant number R01 CA48998, to M.L. Slattery).Harvard cohorts (HPFS, NHS, PHS): HPFS is supported by the NIH (P01 CA055075, UM1 CA167552, U01 CA167552, R01 CA137178, R01 CA151993, R35 CA197735, K07 CA190673, and P50 CA127003), NHS by NIH (R01 CA137178, P01 CA087969, UM1 CA186107, R01 CA151993, R35 CA197735, K07 CA190673, and P50 CA127003), and PHS by the NIH (R01 CA042182).Kentucky: This work was supported by the following grant support: Clinical Investigator Award from Damon Runyon Cancer Research Foundation (CI-8); NCI R01CA136726.MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 509348, 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index and the Australian Cancer Database.MEC: NIH (R37 CA54281, P01 CA033619, and R01 CA063464).MECC: This work was supported by the NIH, U.S. Department of Health and Human Services (grant number R01 CA81488, to S.B. Gruber and G. Rennert).NFCCR: This work was supported by an Interdisciplinary Health Research Team award from the Canadian Institutes of Health Research (CRT 43821); NIH, U.S. Department of Health and Human Serivces (U01 CA74783); and National Cancer Institute of Canada grants (18223 and 18226). The authors acknowledge the contribution of Alexandre Belisle and the genotyping team of the McGill University and Genome Quebec Innovation Centre, Montreal, Canada, for genotyping the Sequenom panel in theNFCCR samples. Funding was provided to M.O. Woods by the Canadian Cancer Society Research Institute.OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CCFR section above. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation.PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, NCI, NIH.PMH: NIH (grant number R01 CA076366, to P.A. Newcomb).VITAL: NIH (K05 CA154337).WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. .