Overwhelming evidence suggests that chronic hepatitis infection is associated with extrahepatic cancers. However, uncertainty persists about the causal role of chronic hepatitis infection on extrahepatic cancers, as much of the current evidence originates from observational studies which are prone to confounding. Herein we performed two-sample Mendelian randomization (MR) to examine the causal associations between chronic hepatitis infection and extrahepatic cancers. Genetic variants associated

more »

... with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection were identified from a genome-wide association study and used as instrumental variables in our analysis. Summary level data for cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, liver, lung, ovary and pancreas were obtained from the Biobank Japan. Using the inverse variance weighted methods, we found chronic HBV infection to be causally associated with gastric cancer (odds ratio [OR] = 1.19 and 95% confidence interval [CI] = 1.13-1.25, P-value = 0.001) and lung cancer (OR = 1.21, 95% CI = 1.14-1.28, P-value = 0.001). Moreover, chronic HBV infection (OR = 1.34, 95% CI = 1.17-1.53, P-value = 0.007) and chronic HCV infection (OR = 2.75, 95% CI = 2.21-3.42, P-value = 0.0008) were all causally associated with liver cancer, supporting a well-established association between chronic hepatitis infection and liver cancer. In conclusions, our MR findings revealed that chronic HBV infection is causally associated with extrahepatic cancers including gastric and lung cancers.