Eight-year follow-up of the 90,000-person Haimen City cohort: I. Hepatocellular carcinoma mortality, risk factors, and gender differences

In an 8-year follow-up of a prospective cohort study in Haimen City, China, we sought to identify hepatocellular carcinoma (HCC) risk factors in addition to hepatitis B virus (HBV) infection. Two cohorts of adults between ages 25 and 64 years at study entry were followed from 1992-1993 to 2000. The male cohort included 58,545 men, 15.0% of whom were HBV carriers. The female cohort included 25,340 women, 10.7% of whom were HBV carriers. 434,718 person-years of follow-up were accumulated, and 1092 deaths from HCC occurred. The relationship of potential risk factors measured at study entry to HCC mortality was analyzed using Cox proportional hazards models. For males, HCC mortality was significantly associated with HBV infection [relative risk (RR) 18.8; 95% confidence interval (CI), 15.7-22.5], history of acute hepatitis (RR, 2.3; 95% CI, 2.0-2.7), family history of HCC (RR, 2.3; 95% CI, 1.9-2.7), and occupation as a peasant (RR, 1.5; 95% CI, 1.3-1.8). For females, HCC mortality was significantly associated with HBV infection (RR, 33.5; 95% CI, 17.1-65.5) and acute hepatitis history (RR, 4.7; 95% CI, 3.0-7.5). HCC risk was not significantly associated with alcohol consumption, water source, or staple foods in either sex. There was no association with smoking in males, but there was a positive association for females. Environmental and genetic risk factors besides HBV infection play a significant role in HCC mortality in this extremely high-risk population. Gender differences in HCC mortality and known risk factors are substantial and warrant further study. Identification of risk factors amenable to intervention should be a high priority in the prevention of HCC.