Journal article
Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
DA Drew, AE Kim, Y Lin, C Qu, J Morrison, JP Lewinger, E Kawaguchi, J Wang, Y Fu, N Zemlianskaia, V Díez-Obrero, SA Bien, N Dimou, D Albanes, JW Baurley, AH Wu, DD Buchanan, JD Potter, RL Prentice, S Harlid Show all
Science Advances | Published : 2024
Abstract
Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influenc..
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Awarded by Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services
Awarded by Center for Inherited Disease Research (CIDR)
Awarded by NIH/NCI Cancer Center Support Grant
Awarded by ORIP grant
Funding Acknowledgements
Individual authors report the following grants and/or funding support: D.A.D.<STRONG>:</STRONG> K01 DK120742; A.E.K.: R01CA201407; J.M.: R01CA201407, P01CA196569; R01CA273198; J.P.L.: R01CA201407, P01CA196569; R01CA273198; E.K.: R01CA201407, P01CA196569; R01CA273198; Y.F.: P01CA196569; R01CA273198; E.L.B.<STRONG>:</STRONG> R01CA059005 and R01CA098286; S.I.B.: Intramural Research Program, Division of Cancer Epidemiology and Genetics, NCI, NIH; J.C.F.: R01 CA155101; S.B.G.: U19 CA148107, R01 CA263318; M.A.J.: U01 CA167551, U01 CA122839, R01 CA143247, U19 CA148107, R01 CA81488, U19 CA148107; B.M.L.: VCA MCRF18005; J.O.: R03CA270473, R01CA207371, R01CA189184,R01CA254108, and U01CA206110; C.M.U.: R03CA270473, R01CA207371, R01CA189184, R01CA254108, U01CA206110, and P30CA042014; U.P.: R01CA059045, U01CA164930, R01CA244588, R01CA201407, and R01 CA273198; W.J.G.: R01CA201407, P01CA196569; R01CA273198; and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO): National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services (R01 CA059045, U01 CA164930, R01 CA244588, R01 CA201407). Genotyping/Sequencing services were provided by the Center for Inherited Disease Research (CIDR) contract number HHSN268201700006I and HHSN268201200008I. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA015704. Scientific Computing Infrastructure at Fred Hutch was funded by ORIP grant S10OD028685. Additional funding supporting the GECCO Consortium and participating studies is listed in the Supplemental Materials.