Dimou NKim AEFlanagan OMurphy NDiez-Obrero VShcherbina AAglago EKBouras ECampbell PTCasey GGallinger SGruber SBJenkins MALin YMoreno VRuiz-Narvaez EStern MCTian YTsilidis KKArndt VBarry ELBaurley JWBerndt SIBézieau SBien SABishop DTBrenner HBudiarto ACarreras-Torres RCenggoro TWChan ATChang-Claude JChanock SJChen XConti DVDampier CHDevall MDrew DAFigueiredo JCGiles GGGsur AHarrison TAHidaka AHoffmeister MHuyghe JRJordahl KKawaguchi EKeku TOLarsson SCLe Marchand LLewinger JPLi LMahesworo BMorrison JNewcomb PANewton CCObon-Santacana MOse JPai RKPalmer JRPapadimitriou NPardamean BPeoples ARPharoah PDPPlatz EAPotter JDRennert GScacheri PCSchoen RESu Y-RTangen CMThibodeau SNThomas DCUlrich CMUm CYvan Duijnhoven FJBVisvanathan KVodicka PVodickova LWhite EWolk AWoods MOQu CKundaje AHsu LGauderman WJGunter MJPeters U2024-08-192024-08-192023-06-26Dimou 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).0007-0920https://mro.massey.ac.nz/handle/10179/71340BACKGROUND: 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.(c) 2023 The Author/sCC BY 4.0https://creativecommons.org/licenses/by/4.0/HumansGene-Environment InteractionGenetic Predisposition to DiseaseRisk FactorsDiabetes MellitusColorectal NeoplasmsPolymorphism, Single NucleotideGenome-Wide Association StudyMicrofilament ProteinsJournal article10.1038/s41416-023-02312-z1532-1827journal-article511-520https://www.ncbi.nlm.nih.gov/pubmed/3736528510.1038/s41416-023-02312-z