Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.502
Peer-review started: June 6, 2014
First decision: June 27, 2014
Revised: July 4, 2014
Accepted: July 30, 2014
Article in press: July 30, 2014
Published online: January 14, 2015
AIM: To identify possible risk factors and their synergism for cholangiocarcinoma development.
METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma (ECC) and 83 intrahepatic cholangiocarcinoma (ICC)], diagnosed at a training hospital in Korea 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 and synergism index, respectively.
RESULTS: There was an association between cholangiocarcinoma and hepatitis B virus (HBV) infection, diabetes mellitus (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). Synergistic interaction was also observed between HBV infection and DM (OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.
CONCLUSION: In this Korean study, 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.
Core tip: Although several risk factors for cholangiocarcinoma were identified in previous studies, details on their interactions or the influence of disease duration on the risk of cholangiocarcinoma are still unclear. Moreover, epidemiologic studies about cholangiocarcinoma in Korea are scarce. The present study in a Korean population showed that the impact of diabetes mellitus on the risk of cholangiocarcinoma was greater when diabetic complications were present. Further, it indicated that there was a synergistic effect between Hepatitis B virus infection and diabetes mellitus on the risk of cholangiocarcinoma, and that the synergistic effect was enhanced in cases of complicated diabetes.