Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk
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- Fangcheng Yuan
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Rayjean J. Hung
- 3Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada.
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- Naomi Walsh
- 4National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland.
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- Han Zhang
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Elizabeth A. Platz
- 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
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- William Wheeler
- 6Information Management Services, Inc., Silver Spring, Maryland.
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- Lei Song
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Alan A. Arslan
- 7Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.
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- Laura E. Beane Freeman
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Paige Bracci
- 11Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
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- Federico Canzian
- 12Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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- Mengmeng Du
- 13Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
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- Steven Gallinger
- 3Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada.
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- Graham G. Giles
- 14Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
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- Phyllis J. Goodman
- 17SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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- Charles Kooperberg
- 18Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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- Loic Le Marchand
- 19Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
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- Rachel E. Neale
- 20Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
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- Jonas Rosendahl
- 21Department of Internal Medicine I, Martin Luther University, Halle, Germany.
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- Ghislaine Scelo
- 22International Agency for Research on Cancer, Lyon, France.
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- Xiao-Ou Shu
- 23Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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- Kala Visvanathan
- 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
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- Emily White
- 24Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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- Wei Zheng
- 23Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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- Demetrius Albanes
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Pilar Amiano
- 25Public Health Division of Gipuzkoa, Ministry of Health of the Basque Government, Donostia-San Sebastian, Spain.
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- Gabriella Andreotti
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Ana Babic
- 28Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- William R. Bamlet
- 29Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
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- Sonja I. Berndt
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Paul Brennan
- 22International Agency for Research on Cancer, Lyon, France.
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- Bas Bueno-de-Mesquita
- 30Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
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- Julie E. Buring
- 34Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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- Peter T. Campbell
- 36Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
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- Stephen J. Chanock
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Charles S. Fuchs
- 37Yale Cancer Center, New Haven, Connecticut.
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- J. Michael Gaziano
- 35Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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- Michael G. Goggins
- 41Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
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- Thilo Hackert
- 42Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
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- Patricia Hartge
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Manal M. Hassan
- 43Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Elizabeth A. Holly
- 11Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
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- Robert N. Hoover
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Verena Katzke
- 44Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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- Holger Kirsten
- 45Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
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- Robert C. Kurtz
- 47Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York.
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- I-Min Lee
- 34Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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- Nuria Malats
- 48Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre, Madrid, Spain.
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- Roger L. Milne
- 14Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
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- Neil Murphy
- 49Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
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- Kimmie Ng
- 28Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Ann L. Oberg
- 29Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
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- Miquel Porta
- 50CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
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- Kari G. Rabe
- 29Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
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- Francisco X. Real
- 52CIBERONC, Madrid, Spain.
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- Nathaniel Rothman
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Howard D. Sesso
- 34Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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- Debra T. Silverman
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Ian M. Thompson
- 55CHRISTUS Santa Rosa Hospital – Medical Center, San Antonio, Texas.
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- Jean Wactawski-Wende
- 56Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.
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- Xiaoliang Wang
- 24Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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- Nicolas Wentzensen
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Lynne R. Wilkens
- 19Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
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- Herbert Yu
- 19Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
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- Anne Zeleniuch-Jacquotte
- 8Department of Population Health, New York University School of Medicine, New York, New York.
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- Jianxin Shi
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Eric J. Duell
- 57Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
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- Laufey T. Amundadottir
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Donghui Li
- 43Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
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- Gloria M. Petersen
- 29Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
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- Brian M. Wolpin
- 28Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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- Harvey A. Risch
- 58Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
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- Kai Yu
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
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- Alison P. Klein
- 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
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- Rachael Stolzenberg-Solomon
- 1Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
Abstract
<jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>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.</jats:p> </jats:sec>
Journal
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- Cancer Research
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Cancer Research 80 (18), 4004-4013, 2020-09-15
American Association for Cancer Research (AACR)
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Keywords
Details 詳細情報について
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- CRID
- 1360576122192549504
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- ISSN
- 15387445
- 00085472
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- Data Source
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- Crossref