Author information
1Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, Florida.
2Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida.
3Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
4CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
5Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
6Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
7Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
8Departments of Obstetrics and Gynecology, Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York.
9Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
10Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
11Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
12Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
13Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada.
14The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
15Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
16Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
17Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
18SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
19Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
20Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
21Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
22Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
23Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
24Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
25Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
26Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
27Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
28Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
29Department of Quantitative Health Sciences, Mayo Clinic College of Medicine, Rochester, Minnesota.
30Yale Cancer Center, New Haven, Connecticut.
31Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
32Smilow Cancer Hospital, New Haven, Connecticut.
33Boston Veteran Affairs Healthcare System, Boston, Massachusetts.
34Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
35Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
36Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
37Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
38Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
39Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York.
40Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
41Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
42Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Spain.
43Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, Madrid, Spain.
44CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, Texas.
45Department of Epidemiology and Environmental Health, University of Buffalo, Buffalo, New York.
46Departments of Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York.
47Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
48Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto, Toronto, Canada.
49Department of Population Science, American Cancer Society, Atlanta, Georgia.
50Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
51Danish Cancer Society Research Center, Copenhagen, Denmark.
52Division of Research, Kaiser Permanente, Northern California, Oakland, California.
53Department of Urology, University of California San Francisco, San Francisco, California.
54Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
55Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
56Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida.
Abstract
Background: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.
Methods: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.
Results: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.
Conclusions: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.
Impact: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.