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Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.

About this Publication
Title
Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.
Pubmed ID
37351909 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Epidemiol Biomarkers Prev. 2023 Sep 1; Volume 32 (Issue 9): Pages 1265-1269
Authors
King SD, Veliginti S, Brouwers MCGJ, Ren Z, Zheng W, Setiawan VW, Wilkens LR, Shu XO, Arslan AA, Beane Freeman LE, Bracci PM, Canzian F, Du M, Gallinger SJ, Giles GG, Goodman PJ, Haiman CA, Kogevinas M, Kooperberg C, LeMarchand L, ...show more Neale RE, Visvanathan K, White E, Albanes D, Andreotti G, Babic A, Berndt SI, Brais LK, Brennan P, Buring JE, Rabe KG, Bamlet WR, Chanock SJ, Fuchs CS, Gaziano JM, Giovannucci EL, Hackert T, Hassan MM, Katzke V, Kurtz RC, Lee IM, Malats N, Murphy N, Oberg AL, Orlow I, Porta M, Real FX, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Yu H, Zeleniuch-Jacquotte A, Yu K, Wolpin BM, Duell EJ, Li D, Hung RJ, Perdomo S, McCullough ML, Freedman ND, Patel AV, Peters U, Riboli E, Sund M, Tjønneland A, Zhong J, Van Den Eeden SK, Kraft P, Risch HA, Amundadottir LT, Klein AP, Stolzenberg-Solomon RZ, Antwi SO
Affiliations
  • Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, Florida.
  • Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida.
  • Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
  • Departments of Obstetrics and Gynecology, Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York.
  • Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
...show more
  • Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada.
  • Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Department of Quantitative Health Sciences, Mayo Clinic College of Medicine, Rochester, Minnesota.
  • Yale Cancer Center, New Haven, Connecticut.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  • Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Spain.
  • Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, Madrid, Spain.
  • CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, Texas.
  • Department of Epidemiology and Environmental Health, University of Buffalo, Buffalo, New York.
  • Departments of Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York.
  • Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
  • Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto, Toronto, Canada.
  • Department of Population Science, American Cancer Society, Atlanta, Georgia.
  • Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
  • Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Division of Research, Kaiser Permanente, Northern California, Oakland, California.
  • Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
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.

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