Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 15, 2020
- Source ID
- 10.1158/0008-5472.can-20-0447
Entities
People
- Alan A Arslan
- Alison P Klein
- Ana Babic
- Ann L Oberg
- Anne Zeleniuch-jacquotte
- Bas Bueno-de-Mesquita
- Brian M. Wolpin
- Charles Kooperberg
- Charles S. Fuchs
- Debra T. Silverman
- Demetrius Albanes
- Donghui Li
- Elizabeth A Platz
- Elizabeth A. Holly
- Emily White
- Eric J Duell
- Fangcheng Yuan
- Fangxing Li
- Federico Canzian
- Francisco X. Real
- Gabriella Andreotti
- Ghislaine Scelo
- Gloria M. Petersen
- Graham Giles
- Han Zhang
- Harvey A. Risch
- Herbert Yu
- Holger Kirsten
- Howard D Sesso
- I-min Lee
- Ian M. Thompson, Jr.
- J. Michael Gaziano
- Jean Wactawski-Wende
- Jianxin Shi
- Jonas Rosendahl
- Julie E. Buring
- Kala Visvanathan
- Kari G Rabe
- Kimmie Ng
- Laufey T. Amundadottir
- Laura E. Beane Freeman
- Lei Song
- Loic Le Marchand
- Lynne R. Wilkens
- Manal M. Hassan
- Mengmeng Du
- Michael Goggins
- Miquel Porta
- Naomi Walsh
- Nathaniel Rothman
- Neil Murphy
- Nicolas Wentzensen
- Nuria Malats
- Paige Bracci
- Patricia Hartge
- Paul Brennan
- Peter R. Leavitt
- Peter T. Campbell
- Phyllis J. Goodman
- Pilar Amiano
- Rachael Z. Stolzenberg-Solomon
- Rachel Neale
- Rayjean J Hung
- Robert C. Kurtz
- Robert N. Hoover
- Roger L. Milne
- Sonja I. Berndt
- Stephen Chanock
- Steven Gallinger
- Thilo Hackert
- Verena A Katzke
- Wei Xing Zheng
- William Bamlet
- William Wheeler
- Xiao-Ou Shu
Organizations
- American Cancer Society
- Autonomous University of Barcelona
- Bellvitge Biomedical Research Institute
- California Department of Public Health
- Cancer Council Victoria
- Czech Science Foundation
- Dana–Farber Cancer Institute
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Dublin City University
- European Cooperation in Science and Technology
- Fred Hutchinson Cancer Center
- German Cancer Research Center
- Harvard Medical School
- Harvard University
- Heidelberg University
- Imperial College London
- International Agency for Research on Cancer
- Johns Hopkins Bloomberg School of Public Health
- Johns Hopkins School of Medicine
- Leiden University Medical Center
- Leipzig University
- Lustgarten Foundation for Pancreatic Cancer Research
- Martin Luther University Halle-Wittenberg
- Mayo Medical School
- Memorial Sloan Kettering Cancer Center
- Ministry of Health of Italy
- Ministry of Health of the Czech Republic
- Ministry of Science and Technology
- National Cancer Institute
- National Center for Oncological Research
- National Health and Medical Research Council
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Institute for Health and Care Research
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- National Institute on Drug Abuse
- National Institutes of Health
- Netherlands National Institute for Public Health and the Environment
- Pancreatic Cancer Action Network
- Pompeu Fabra University
- QIMR Berghofer Medical Research Institute
- United States Department of Defense
- United States Department of Health and Human Services
- Universiti Malaya
- University at Buffalo
- University of California, San Francisco
- University of Melbourne
- University of Texas at Austin
- University of Toronto
- Vanderbilt University
- Yale School of Medicine
- Yale School of Public Health