Risk of Hepatocellular Carcinoma and Habits of Alcohol Drinking, Betel Quid Chewing and Cigarette Smoking: A Cohort of 2416 HBsAg-Seropositive and 9421 HBsAg-Seronegative Male Residents in Taiwan

Objectives: Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC) in the world. The specific aim of this study is to assess the associations between the risk of HCC and habits of alcohol drinking, betel quid chewing and cigarette smoking among subjects with and without chronic HBV infection. Methods: A total of 11,837 male residents in Taiwan were recruited in this community-based cohort study. Hepatitis B surface antigen (HBsAg) and antibody against hepatitis C virus (anti-HCV) in serum were determined by enzyme immunoassay, and the habits of alcohol drinking, betel quid chewing and cigarette smoking were collected through standardized personal interview according to a structured questionnaire. During the follow-up period of 91,885 person-years, 115 incident HCC cases were identified through data linkage with national cancer registry profile. The relative risk (RR) of developing HCC for habits of various substance use and chronic HBV infection were estimated by Cox's proportional hazards regression analyses. Results: Significantly increased HCC risk was observed for seropositives of HBsAg or anti-HCV, alcohol drinkers, betel quid chewers and cigarette smokers. There was a significant dose-response relationship between the risk of HCC and the number of habits of substance use. The highest multivariate-adjusted HCC risk was observed among HBsAg-seropositive substance users (RRs: 17.9-26.9), followed by HBsAg-seropositive non-users (RRs: 13.1-19.2), HBsAg-seronegative substance users (RRs: 1.6-2.7) and HBsAg-seronegative non-users (referent with RR = 1). The multivariate-adjusted relative HCC risks for habits of use of various substances were more profound among HBsAg-seronegatives than HBsAg-seropositive ones. Conclusion: Habitual alcohol drinking, betel quid chewing and cigarette smoking are associated with an increased risk of HCC. Abstinence from substance use is important for the prevention of HCC in areas where chronic HBV infection is endemic.