| Literature DB >> 32641412 |
Fangcheng Yuan1,2, Rayjean J Hung3, Naomi Walsh4, Han Zhang1, Elizabeth A Platz2,5, William Wheeler6, Lei Song1, Alan A Arslan7,8,9,10, Laura E Beane Freeman1, Paige Bracci11, Federico Canzian12, Mengmeng Du13, Steven Gallinger3, Graham G Giles14,15,16, Phyllis J Goodman17, Charles Kooperberg18, Loic Le Marchand19, Rachel E Neale20, Jonas Rosendahl21, Ghislaine Scelo22, Xiao-Ou Shu23, Kala Visvanathan2,5, Emily White24, Wei Zheng23, Demetrius Albanes1, Pilar Amiano25,26,27, Gabriella Andreotti1, Ana Babic28, William R Bamlet29, Sonja I Berndt1, Paul Brennan22, Bas Bueno-de-Mesquita30,31,32,33, Julie E Buring34,35, Peter T Campbell36, Stephen J Chanock1, Charles S Fuchs37,38,39, J Michael Gaziano35,40, Michael G Goggins41, Thilo Hackert42, Patricia Hartge1, Manal M Hassan43, Elizabeth A Holly11, Robert N Hoover1, Verena Katzke44, Holger Kirsten45,46, Robert C Kurtz47, I-Min Lee34,35, Nuria Malats48, Roger L Milne14,15,16, Neil Murphy49, Kimmie Ng28, Ann L Oberg29, Miquel Porta50,51, Kari G Rabe29, Francisco X Real52,53,54, Nathaniel Rothman1, Howard D Sesso34,35, Debra T Silverman1, Ian M Thompson55, Jean Wactawski-Wende56, Xiaoliang Wang24, Nicolas Wentzensen1, Lynne R Wilkens19, Herbert Yu19, Anne Zeleniuch-Jacquotte8,9,10, Jianxin Shi1, Eric J Duell57, Laufey T Amundadottir1, Donghui Li43, Gloria M Petersen29, Brian M Wolpin28, Harvey A Risch58, Kai Yu1, Alison P Klein2,5,41, Rachael Stolzenberg-Solomon59.
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. ©2020 American Association for Cancer Research.Entities:
Mesh：
Year: 2020 PMID： 32641412 PMCID： PMC7861352 DOI： 10.1158/0008-5472.CAN-20-0447
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701