Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.
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Date
2023-06-26
Open Access Location
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature
Rights
(c) 2023 The Author/s
CC BY 4.0
CC BY 4.0
Abstract
BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis.
METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test).
RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09).
DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.
Description
Keywords
Humans, Gene-Environment Interaction, Genetic Predisposition to Disease, Risk Factors, Diabetes Mellitus, Colorectal Neoplasms, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Microfilament Proteins
Citation
Dimou N, Kim AE, Flanagan O, Murphy N, Diez-Obrero V, Shcherbina A, Aglago EK, Bouras E, Campbell PT, Casey G, Gallinger S, Gruber SB, Jenkins MA, Lin Y, Moreno V, Ruiz-Narvaez E, Stern MC, Tian Y, Tsilidis KK, Arndt V, Barry EL, Baurley JW, Berndt SI, Bézieau S, Bien SA, Bishop DT, Brenner H, Budiarto A, Carreras-Torres R, Cenggoro TW, Chan AT, Chang-Claude J, Chanock SJ, Chen X, Conti DV, Dampier CH, Devall M, Drew DA, Figueiredo JC, Giles GG, Gsur A, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Jordahl K, Kawaguchi E, Keku TO, Larsson SC, Le Marchand L, Lewinger JP, Li L, Mahesworo B, Morrison J, Newcomb PA, Newton CC, Obon-Santacana M, Ose J, Pai RK, Palmer JR, Papadimitriou N, Pardamean B, Peoples AR, Pharoah PDP, Platz EA, Potter JD, Rennert G, Scacheri PC, Schoen RE, Su Y-R, Tangen CM, Thibodeau SN, Thomas DC, Ulrich CM, Um CY, van Duijnhoven FJB, Visvanathan K, Vodicka P, Vodickova L, White E, Wolk A, Woods MO, Qu C, Kundaje A, Hsu L, Gauderman WJ, Gunter MJ, Peters U. (2023). Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.. Br J Cancer. 129. 3. (pp. 511-520).