Chemoprevention of hepatocellular carcinoma: A randomized, double-blind trial in Linxian, China.

B145

We examined the effect of supplementation with four different combinations of vitamins and minerals on the prevention of hepatocellular carcinoma (HCC) mortality among 29,450 healthy adults from a nutrient-inadequate population in Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo daily for 5 ¼ years. The combinations tested in this trial were: factor A = retinol and zinc; factor B = riboflavin and niacin; factor C = ascorbic acid and molybdenum; factor D = beta-carotene, alpha-tocopherol, and selenium. All doses were 1-2 times US RDAs. HCC deaths (n = 151) identified during the trial period (1986 - 1991) and ten years after the trial ended (1991 - 2001) were the study outcome. No significant differences in HCC death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P-values >0.20), or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. However, age and sex significantly modified the effects of the supplements. Factor A and factor B significantly reduced the risk of HCC death in individuals younger than 55 years of age at randomization (P = 0.049 and 0.025, respectively) but not in individuals ≥ 55 years of age (P = 0.79 and 0.57, respectively). Factor C marginally significantly reduced the risk of HCC death in males (P = 0.058) but not in females (P = 0.37). Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5 ¼ years reduced HCC mortality in certain subgroups of this nutrient-inadequate population in Linxian, China.