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

Fangcheng Yuan, Rayjean J. Hung, Naomi Walsh, Han Zhang, Elizabeth A. Platz, William Wheeler, Lei Song, Alan A. Arslan, Laura E. Beane Freeman, Paige Bracci, Federico Canzian, Mengmeng Du, Steven Gallinger, Graham G. Giles, Phyllis J. Goodman, Charles Kooperberg, Loic Le Marchand, Rachel E. Neale, Jonas Rosendahl, Ghislaine SceloXiao Ou Shu, Kala Visvanathan, Emily White, Wei Zheng, Demetrius Albanes, Pilar Amiano, Gabriella Andreotti, Ana Babic, William R. Bamlet, Sonja I. Berndt, Paul Brennan, Bas Bueno-De-Mesquita, Julie E. Buring, Peter T. Campbell, Stephen J. Chanock, Charles S. Fuchs, J. Michael Gaziano, Michael G. Goggins, Thilo Hackert, Patricia Hartge, Manal M. Hassan, Elizabeth A. Holly, Robert N. Hoover, Verena Katzke, Holger Kirsten, Robert C. Kurtz, I. Min Lee, Nuria Malats, Roger L. Milne, Neil Murphy, Kimmie Ng, Ann L. Oberg, Miquel Porta, Kari G. Rabe, Francisco X. Real, Nathaniel Rothman, Howard D. Sesso, Debra T. Silverman, Ian M. Thompson, Jean Wactawski-Wende, Xiaoliang Wang, Nicolas Wentzensen, Lynne R. Wilkens, Herbert Yu, Anne Zeleniuch-Jacquotte, Jianxin Shi, Eric J. Duell, Laufey T. Amundadottir, Donghui Li, Gloria M. Petersen, Brian M. Wolpin, Harvey A. Risch, Kai Yu, Alison P. Klein, Rachael Stolzenberg-Solomon

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1 Scopus citations

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 x 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 ¼ 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P ¼ 0.22) and primary sclerosing cholangitis (P ¼ 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.

Original languageEnglish (US)
Pages (from-to)4004-4013
Number of pages10
JournalCancer research
Volume80
Issue number18
DOIs
StatePublished - Sep 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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