Association of serum α-tocopherol, β-carotene, and retinol with liver cancer incidence and chronic liver disease mortality

Background: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum alpha-tocopherol, beta-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. Methods: Baseline and 3-year follow-up serum were available from 29 046 and 22 805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. Results: Higher beta-carotene and retinol levels were associated with less liver cancer (beta-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend = 0.0009) and CLD mortality (beta-carotene: 0.47, 0.30-0.75, P-trend = 0.001; retinol: 0.55, 0.38-0.78, P-trend = 0.0007). alpha-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend = 0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend = 0.77). Participants with higher levels of beta-carotene and retinol, but not alpha-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. Conclusions: Our findings suggest that higher concentrations of beta-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.