biostudies-literatureMocci EKaiser Permanente and Group Health CooperativeCancer Council VictoriaWexler Family FundGeoffrey Beene FoundationNHMRC Senior Research FellowshipNIEHS NIH HHSNHLBI NIH HHSPromises for PurpleItalian Association for Research on CancerCzech Science FoundationGeneralitat de CatalunyaCalifornia Department of Public HealthAmerican Cancer SocietyNoble Effort FundRed temática de investigación cooperativa de centros en Epidemiología y salud públicaSusan Wojcicki and Dennis TroperRed temática de investigación cooperativa de centros en CáncerPeter R. Leavitt Family FundCIBER de EpidemiologíaRed Temática de Investigación Cooperativa en Cáncer, SpainNational Program of Cancer Registries of the Centers for Disease Control and PreventionIntramural NIH HHSItalian Ministry of ResearchWorld Health OrganizationMinisterio de Ciencia y TecnologíaArnold and Arlene Goldstein Family FoundationPatient-Centered Outcomes Research InstituteHHS | National Institutes of HealthMaryland Cigarette Restitution FundFondo de Investigaciones SanitariasHHS | NIH | National Cancer InstituteMinistry of Health of the Czech RepublicPancreatic Cancer Action NetworkLustgarten FoundationHHS | NIH | National Human Genome Research InstituteSol Goldman Pancreas Cancer Research CenterItalian Ministry of HealthBundesministerium für Bildung und ForschungNCCDPHP CDC HHSAustralian National Health and Medical Research CouncilHHS | NIH | National Institutes of Environmental Health SciencesU.S. Department of Health and Human ServicesCDC&apos;s National Program of Cancer RegistriesSociety of MSKCCEuropean Cooperation in Science and TechnologyHHS | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer InstituteNational Health and Medical Research Council of AustraliaJoan Rombauer Pancreatic Cancer FundInternal Grant Agency of the Czech Ministry of HealthInstituto de Salud Carlos III-FEDERFondo de Investigación SanitariaU.S. Department of DefenseNHGRI NIH HHSNCI NIH HHS3134-3143https://www.ebi.ac.uk/biostudies/studies/S-EPMC8178175biostudies-literatureUnknown81(11)Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and <i>P</i> < 5 × 10^-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMCancer researchSmoking Modifies Pancreatic Cancer Risk Loci on 2q21.3.PMC8178175U10 CA37429MH CZ-DRO-MMCI 00209805CA182913R01 CA098870ZIA CP010193U01 CA074783P301/12/1734HL-08046701EY1101HHSN268201600003CHL-099355R01 CA154823P30 ES000260CIRIT - SGRR03 CA123546C03/09CA-40360209057CICYT SAF 2000-0097U01 CA247283P01 CA87969R01 CA040360HL-26490001442302NR9998-3P30 CA015083RD12/0036/00501060183HHSN268201600004CR01 CA49449UM1 CA182910BM1204UM1 CA182913UM1 CA173640RC1203GA57R01 CA034944UM1 CA167552PI15/01573HSN261201000140C01GS08114C03/10HL-3459595/001712 CUP_J33G13000210001R01 HL080467R01 CA047988CA-34944U01 CA182913R03 CA123546-02CA130288R01 CA097075R01 CA097193RC1303GA54RC1303GA53R01 HL034595RC1303GA50U58DP003862-01UM1 CA182883HHSN268201600018CR01CA109767-S1UM1CA173640UM1 CA182934396414R01 HL043851P01 CA087969R0CA059706UM1CA182910Z99 CA999999U58 DP003862U01 CA182934HHSN261200800001EUG1 CA189974R01CA1009767ME-1602-34530RO1 CA102765FIRB - RBAP10AHJBR01 CA098661NR 9029-4/2006PI13/000821074383R01 CA109767R01 HG010480U01 CA182883R01 HG010480-01UM1 CA186107HL-043851N/AP30 CA008748R01 CA049449RO1 CA154823U01 CA167551R01 CA102765P50 CA0629245R01CA098870P30 CA016087NR9422-3CA-047988HHSN268201600001CR01 HL02649012182R01 CA97075IGA NT 13 263P50 CA102701RC1 HL099355HHSN268201600002CU01 CA21017U10 CA037429CA-097193Giovannucci ELThompson IMSesso HDHartge PWactawski-Wende JNeale REStrobel OChatterjee NScelo GBerndt SIOberg ALLe Marchand LTrichopoulou ATjonneland ARothman NAndreotti GVisvanathan KPeters UHolly EAJacobs EJZeleniuch-Jacquotte AStolzenberg-Solomon RHassan MMVan Den Eeden SKBracci PMChanock SJBrennan PMilne RLLi DBuring JEMocci EZheng WArslan AARabe KGYuan FWolpin BMLee IMAmundadottir LTKurtz RCGoodman PJKraft PBlackford ALChilds EJDu MCanzian FGoggins MGYu HSilverman DTWheeler WBeane-Freeman LEPorta MGallinger SHoover RNHung RJGiles GGMalats NPetersen GMWhite ERiboli ENg KBamlet WRShu XOBabic AKlein APBueno-de-Mesquita BPanico SWilkens LRKundu PAlbanes DWentzensen NDuell EJRisch HAKooperberg CFuchs CSStevens VLGaziano JMCampa DfalseSmoking Modifies Pancreatic Cancer Risk Loci on 2q21.3.Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and <i>P</i> < 5 × 10^-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TM2021-01-01T00:00:00Z2021 Jun2026-05-07T20:24:48.621Z2022-02-11T13:23:17.053ZS-EPMC81781753357408810.1158/0008-5472.can-20-326710.1158/0008-5472.CAN-20-3267