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Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk

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dc.contributor.author Yuan, Fangcheng
dc.contributor.author Porta Serra, Miquel
dc.contributor.author Real, Francisco X.
dc.contributor.author Stolzenberg-Solomon, Rachael Z.
dc.date.accessioned 2023-03-27T08:19:06Z
dc.date.available 2023-03-27T08:19:06Z
dc.date.issued 2020
dc.identifier.citation Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W et al. Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk. Cancer Res. 2020;80(18):4004-13. DOI: 10.1158/0008-5472.CAN-20-0447
dc.identifier.issn 0008-5472
dc.identifier.uri http://hdl.handle.net/10230/56354
dc.description.abstract Registry-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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Association for Cancer Research (AACR)
dc.relation.ispartof Cancer Res. 2020;80(18):4004-13
dc.rights © American Association for Cancer Research (AACR) http://dx.doi.org/10.1158/0008-5472.CAN-20-0447
dc.title Genome-wide association study data reveal genetic susceptibility to chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma risk
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1158/0008-5472.CAN-20-0447
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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