Previous studies evaluating the association between smoking and risk of cholangiocarcinoma (CCA) have yielded controversial results. We conducted a meta-analysis to evaluate the association based on available evidence. We searched the databases of Embase, PubMed and Cochrane Central Register of Controlled Trials from inception to April 11, 2017. Studies that investigated the association between smoking and risk of CCA were included. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using either a random-effects or a fixed-effects model. A total of 22 studies involving 324,333 participants were identified. The summary OR of CCA was 1.31 (95% CI, 1.15 to 1.51) for smokers versus nonsmokers. The increased risk was independent of diabetes mellitus, bilious tract stone disease, and liver cirrhosis. Smokers also had increased risk of intrahepatic CCA (12 studies; OR, 1.31; 95% CI, 1.06 to 1.63) and extrahepatic CCA (12 studies; OR, 1.32; 95% CI, 1.10 to 1.59) compared with nonsmokers. The results of our meta-analysis support the hypothesis that there is a moderate association between cigarette smoking and risk of CCA.

To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma (ECC) through a meta-analysis of clinical observational studies.

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.

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.

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.