title: Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: a case-control study in Korea.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Ban Seok
authors.initials: BS
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Chung Mo
authors.initials: CM
authors.lastname: Nam
authors.affiliation: 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.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Roh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000453:epidemiology*; D001653:Bile Ducts, Intrahepatic; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000453:epidemiology*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006509:Hepatitis B / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors
keywords: Cholangiocarcinoma; Diabetes mellitus; Hepatitis; Risk factor; Synergism