Funding
Division of Cancer Epidemiology and Genetics
NCI
NIH
Ministry of Health of the Czech Republic
Lustgarten Foundation
Sol Goldman Pancreas Cancer Research Center
National Health and Medical Research Council of Australia
NHMRC Senior Research Fellowship
California Department of Public Health
CDC's National Program of Cancer Registries
Czech Science Foundation
Internal Grant Agency of the Czech Ministry of Health
Heidelberger EPZ-Pancobank
BMBF
BMBH
Italian Ministry of Health
Italian Association for Research on Cancer
Italian Ministry of Research
Italian FIMP-Ministry of Health
National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, UK
VicHealth and Cancer Council Victoria
Cancer Council Victoria
NYU Women's Health Study
Instituto de Salud Carlos III-FEDER, Spain
Fondo de Investigaciones Sanitarias
Red Temática de Investigación Cooperativa en Cáncer, Spain
European Cooperation in Science and Technology
Ministerio de Ciencia y Tecnología
Fondo de Investigación Sanitaria
Madrid, Spain; Generalitat de Catalunya
‘Red temática de investigación cooperativa de centros en Cáncer’
‘Red temática de investigación cooperativa de centros en Epidemiología y salud pública’
CIBER de Epidemiología
CIBERESP
Women's Health Study
Hale Center for Pancreatic Cancer Research
United States Department of Defense
Pancreatic Cancer Action Network
Noble Effort Fund
Peter R. Leavitt Family Fund
Wexler Family Fund
Broman Family Fund for Pancreatic Cancer Research
Bob Parsons Fellowship
National Heart, Lung, and Blood Institute
U.S. Department of Health and Human Services
NHGRI
NHLBI
NIDA
NIMH
NINDS
ARTICLE 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.
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.
