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

Background: There are conflicting dataon 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 ¼ 5,090, controls n ¼ 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n ¼ 4,163, controls n ¼ 3,792) were analyzed.Weused dataon68genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separatelyto predict genetic heritability of NAFLD. We then assessed the relationship between eachofthe fourMRmethods andpancreatic 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.