Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2015; 21(2): 502-510
Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.502
Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A case-control study in Korea
Ban Seok Lee, Eun-Cheol Park, Seung Woo Park, Chung Mo Nam, Jaehoon Roh
Ban Seok Lee, Eun-Cheol Park, Seung Woo Park, Chung Mo Nam, Jaehoon Roh, Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul 120-752, South Korea
Ban Seok Lee, Digestive Disease Center and Department of Internal Medicine, Cheju Halla General Hospital, Jeju 690-766, South Korea
Eun-Cheol Park, Chung Mo Nam, Jaehoon Roh, Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea
Eun-Cheol Park, Institute of Health Services Research, Yonsei University College of Medicine, Seoul 120-752, South Korea
Seung Woo Park, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea
Author contributions: Roh J and Park EC contributed to the study concept and design; Lee BS and Nam CM contributed to the analysis and interpretation of data, and statistical analysis; Lee BS drafted the manuscript; Roh J, Park EC and Park SW performed critical revision of the manuscript for important intellectual content, and contributed to the study supervision.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jaehoon Roh, MD, PhD, Department of Preventive Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea. jhroh@yuhs.ac
Telephone: +82-2-22281867 Fax: +82-2-3928133
Received: June 6, 2014
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
Processing time: 226 Days and 4 Hours
Abstract

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.

Keywords: Cholangiocarcinoma; Risk factor; Hepatitis; Synergism; Diabetes mellitus

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.