title: Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma: a meta-analysis.
abstract: OBJECTIVE
  To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma (ECC) through a meta-analysis of clinical observational studies.
  
  
  METHODS
  A literature search was conducted using Embase and MEDLINE databases from inception to 31 May 2013 without language limitations, and by manually searching the references of retrieved articles. Case-control and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included. The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale. Summary relative risks and corresponding 95%CI were calculated using a random-effects model. Publication bias was assessed by Begg's funnel plot and Egger's test.
  
  
  RESULTS
  A total of 12 eligible articles (11 case-control studies and one cohort study) were included in this meta-analysis. Eleven studies reported the association between smoking and ECC. Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers (summary RR = 1.23; 95%CI: 1.01-1.50). This correlation was present in population-based studies (n = 5; summary RR = 1.47; 95%CI: 1.06-2.05) but not in hospital-based studies (n = 6; summary RR = 1.10; 95%CI: 0.88-1.37) and in non-Asian regions (n = 7; summary RR = 1.39; 95%CI: 1.03-1.87) but not in Asia (n = 4; summary RR = 1.08; 95%CI: 0.85-1.38). Seven studies reported an association between consuming alcohol and ECC. Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol (summary RR = 1.09; 95%CI: 0.87-1.37). There was moderate heterogeneity among the studies and no evidence of publication bias.
  
  
  CONCLUSIONS
  Smoking is associated with an increased risk of ECC, but alcohol consumption is not. Further population-based studies, particularly cohort studies, are warranted to enable definitive conclusions.
authors.affiliation: Xiao-Hua Ye, Jin Ding, Yan-Ping Chen, Department of Gastroenterology and Hepatology, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Ye
authors.affiliation: Xiao-Hua Ye, Jin Ding, Yan-Ping Chen, Department of Gastroenterology and Hepatology, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China.
authors.forename: Jia-Ping
authors.initials: JP
authors.lastname: Huai
authors.affiliation: Xiao-Hua Ye, Jin Ding, Yan-Ping Chen, Department of Gastroenterology and Hepatology, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ding
authors.affiliation: Xiao-Hua Ye, Jin Ding, Yan-Ping Chen, Department of Gastroenterology and Hepatology, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Chen
authors.affiliation: Xiao-Hua Ye, Jin Ding, Yan-Ping Chen, Department of Gastroenterology and Hepatology, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China.
authors.forename: Xue-Cheng
authors.initials: XC
authors.lastname: Sun
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D001650:Bile Duct Neoplasms / Q000453:epidemiology*; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000453:epidemiology*; D006801:Humans; D016017:Odds Ratio; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
keywords: Alcohol consumption; Extrahepatic cholangiocarcinoma; Meta-analysis; Relative risk; Smoking