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Supplementary Tables from Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

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posted on 2023-03-31, 03:40 authored by 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 Scelo, Xiao-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

The file contains supplementary tables S1, S2, S3, S4, S5, S6, and S7.

Funding

Division of Cancer Epidemiology and Genetics

NCI

NIH

Ministry of Health of the Czech Republic

Lustgarten Foundation

Sol Goldman Pancreas Cancer Research Center

Mayo Clinic SPORE in Pancreatic Cancer

National Cancer Institute

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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

History

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.

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