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

Abstract

Background: 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. Methods: 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. Results: 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 nonsignificant 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. Conclusion: Our findings suggest that smoking increases IHBDC risk in men, especially among regular drinkers.

Should we consider gallbladder cancer a new smoking‐related cancer? A comprehensive meta‐analysis focused on dose–response relationships

“…Thus, 20 original articles were included in the present meta‐analysis. Supplementary Tables S2 and S3 summarize the main characteristics of these case–control ( n = 11) and cohort studies ( n = 9) . The original articles were published between 1990 and 2019, and were based on 4,676 gallbladder cancer cases.…”

“…The original articles were published between 1990 and 2019, and were based on 4,676 gallbladder cancer cases. In all, 10 studies provided a measure of association (or provided information to derive it) for current smokers, 9 for former smokers and 18 for ever smokers, compared to never smokers. Four studies reported RRs for smoking intensity and three for smoking duration for current smokers, and one study reported RRs for time since quitting for former smokers…”

“…Supplementary Tables S2 and S3 summarize the main characteristics of these case-control (n = 11) [29][30][31][32][33][34][35][36][37][38][39] and cohort studies (n = 9). [40][41][42][43][44][45][46][47][48] The original articles were published between 1990 and 2019, and were based on 4,676 gallbladder cancer cases. In all, 10 studies provided a measure of association (or provided information to derive it) for current smokers, 29,38,[40][41][42][43][44][45][46][47] 9 for former smokers 29,38,[40][41][42][43][44]46,47 and for ever smokers, [29][30][31][32][33][34][35][36][37]…”

“…Our meta‐analysis, considered eight additional cohort studies, three already published before the meta‐analysis by Wenbin and colleagues, satisfying their eligibility criteria . Three further studies were already available but did not consider only gallbladder cancer, so were ineligible according to Wenbin's criteria, and only two are more recent . We also considered four additional case–control studies on smoking and gallbladder cancer risk published after 2013, thus adding value to our meta‐analysis.…”

Cholangiocarcinoma: Epidemiology and risk factors

“…100 Another prospective cohort study in Japan reported a HR = 1.96 (95% CI 0.99-3.91) for iCCA in regular drinkers consuming ≥300 g/day of ethanol, compared to non-drinkers; however, these results did not reach statistical significance (P-trend = 0.065), probably because of the small number of iCCA cases included. 101 Whether the association between alcohol consumption and iCCA is related to liver disease (i.e. alcoholic liver disease and cirrhosis), or to other underlying carcinogenic mechanisms is unclear.…”