Background: Liver cancer is one of the most common cancers worldwide, particularly in Asia and Africa, where infectious hepatitis and aflatoxin exposures are common. We conducted a prospective cohort study of liver cancer in Korea to assess the independent effects and interactions of smoking, alcohol consumption, and hepatitis B on risk of mortality from hepatocellular carcinoma.

Methods: From a total of 1,283,112 men and women free of cancer at baseline, 3807 died from liver cancer during follow-up from 1993 to 2002. All participants reported their smoking and alcohol consumption, and hepatitis B surface antigen (HBsAg) status was documented for 47.2% of the participants. Relative risk and 95% confidence intervals (CIs) of mortality from hepatocellular carcinoma were calculated using proportional hazards models adjusted for age, alcohol drinking, diabetes, and HBsAg status.

Results: Current smoking was associated with increased risk of mortality from hepatocellular carcinoma in men (RR = 1.4; 95% CI = 1.3 to 1.6) but not women (RR = 1.1; CI = 0.8 to 1.7). The relative risk of mortality from hepatocellular carcinoma for male HBsAg carriers was 24.3 (95% CI = 21.9 to 26.9) times that in HBsAg-negative males; the relative risk for HBsAg-positive women was 54.4 (95% CI = 24.8 to 119.5). Heavy alcohol drinking was associated with hepatocellular carcinoma mortality risk in the subgroup of men who were tested for HBsAg (RR =1.5; 95% CI = 1.2 to 2.0). There was no interaction among smoking, alcohol drinking, and HBsAg in terms of hepatocellular carcinoma mortality.

Conclusion: Cigarette smoking, heavy alcohol consumption, and HBsAg were independently associated with increased risk of mortality from hepatocellular carcinoma but did not interact synergistically. The relatively higher increase in mortality from hepatocellular carcinoma in HBsAg-seropositive women compared with men merits further research.