Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer

Smoking and alcohol are established risk factors for several types of cancer, but the effects on biliary cancers, comprising biliary tract cancer (BTC) and intrahepatic bile duct cancer (IHBDC), have been inconclusive.In this population-based prospective cohort study in Japan, we investigated the association of smoking and alcohol consumption with the risks of BTC and its subtypes and IHBDC incidence in men and women. Furthermore, the association of smoking stratified by drinking status was investigated. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model.A total of 48,367 men and 54,776 women aged 40-69 years were enrolled from 1990 through 1994 and followed up for 846,417 person-years in men and 1,021,330 person-years in women until 2012, during which 246 BTC and 80 IHBDC male cases and 227 BTC and 60 IHBDC female cases were identified. In men, smoking was significantly associated with an increased risk of IHBDC (HR 2.25; 95% CI, 1.19-4.25 for current smokers with ≥30 pack-years compared with non-smokers), and the risk was enhanced among regular drinkers compared with non/occasional-drinkers (HR 3.48; 95% CI, 1.41-8.61). A non-significant increase of IHBDC risk associated with alcohol was observed. Neither smoking nor alcohol consumption was associated with BTC risk. In women, the association of smoking and alcohol consumption with IHBDC and BTC was unclear because current smokers and regular drinkers were very few.Our findings suggest that smoking increases IHBDC risk in men, especially among regular drinkers.