Risk factors for cholangiocarcinoma : synergism of hepatitis B virus infection and diabetes mellitus

Abstract

Purpose: Recent investigations have identified several risk factors, including hepatitis B virus (HBV) infection and diabetes mellitus (DM), for cholangiocarcinoma. However, the synergisms between these risk factors are not well known. This study was conducted to evaluate risk factors for cholangiocarcinoma and possible synergism between thesefactors.Materials and Methods: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients (193 extrahepatic cholangiocarcinoma [ECC] and 83 intrahepatic cholangiocarcinoma [ICC]), diagnosed between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression analysis and synergism index estimation, respectively.Results: There was an association between cholangiocarcinoma and HBV infection, DM, cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios (aORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM (aOR 12.2; 95% CI:1.9–80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC (aOR 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC (aOR 8.6, 157.4, 5.3, and 4.9, respectively). Synergisticinteraction was also observed between HBV infection and DM (aOR 22.7; 95% CI: 2.4–214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.Conclusion: HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanisms for such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.