Yuan, FangchengHung, Rayjean JWalsh, NaomiZhang, HanPlatz, Elizabeth AWheeler, WilliamSong, LeiArslan, Alan ABeane Freeman, Laura EBracci, PaigeCanzian, FedericoDu, MengmengGallinger, StevenGiles, Graham GGoodman, Phyllis JKooperberg, CharlesLe Marchand, LoicNeale, Rachel ERosendahl, JonasScelo, GhislaineShu, Xiao-OuVisvanathan, KalaWhite, EmilyZheng, WeiAlbanes, DemetriusAmiano, PilarAndreotti, GabriellaBabic, AnaBamlet, William RBerndt, Sonja IBrennan, PaulBueno-de-Mesquita, BasBuring, Julie ECampbell, Peter TChanock, Stephen JFuchs, Charles SGaziano, J MichaelGoggins, Michael GHackert, ThiloHartge, PatriciaHassan, Manal MHolly, Elizabeth AHoover, Robert NKatzke, VerenaKirsten, HolgerKurtz, Robert CLee, I-MinMalats, NuriaMilne, Roger LMurphy, NeilNg, KimmieOberg, Ann LPorta, MiquelRabe, Kari GReal Arribas, FranciscoRothman, NathanielSesso, Howard DSilverman, Debra TThompson, Ian MWactawski-Wende, JeanWang, XiaoliangWentzensen, NicolasWilkens, Lynne RYu, HerbertZeleniuch-Jacquotte, AnneShi, JianxinDuell, Eric JAmundadottir, Laufey TLi, DonghuiPetersen, Gloria MWolpin, Brian MRisch, Harvey AYu, KaiKlein, Alison PStolzenberg-Solomon, Rachael2024-02-132024-02-132020-09-15Cancer Res . 2020 ;80(18):4004-4013http://hdl.handle.net/20.500.12105/18190Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Genetic Predisposition to DiseaseCarcinoma, Pancreatic DuctalCase-Control StudiesCeliac DiseaseCholangitis, SclerosingChronic DiseaseColitis, UlcerativeCrohn DiseaseGenome-Wide Association StudyHumansInflammatory Bowel DiseasesPancreatic NeoplasmsPancreatitis, ChronicAttribution-NonCommercial-NoDerivatives 4.0 Internacional326414128018400410.1158/0008-5472.CAN-20-04471538-7445Cancer researchhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861352/open access