Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk.
Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, Song L, Arslan AA, Beane Freeman LE, Bracci P, Canzian F, Du M, Gallinger S, Giles GG, Goodman PJ, Kooperberg C, Le Marchand L, Neale RE, Rosendahl J, Scelo G, Shu XO, Visvanathan K, White E, Zheng W, Albanes D, Amiano P, Andreotti G, Babic A, Bamlet WR, Berndt SI, Brennan P, Bueno-de-Mesquita B, Buring JE, Campbell PT, Chanock SJ, Fuchs CS, Gaziano JM, Goggins MG, Hackert T, Hartge P, Hassan MM, Holly EA, Hoover RN, Katzke V, Kirsten H, Kurtz RC, Lee IM, Malats N, Milne RL, Murphy N, Ng K, Oberg AL, Porta M, Rabe KG, Real FX, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Wilkens LR, Yu H, Zeleniuch-Jacquotte A, Shi J, Duell EJ, Amundadottir LT, Li D, Petersen GM, Wolpin BM, Risch HA, Yu K, Klein AP, Stolzenberg-Solomon R
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.
- 2006-0306: Whole Genome Scan of Incident Pancreatic Cancer in the Cohort Consortium (PanScan) (Rachael Stolzenberg-Solomon - 2006)