Association of serum α-tocopherol, β-carotene and retinol with subsequent liver cancer incidence and chronic liver disease mortality in the ATBC Study
Gabriel Y. Lai1,2, Stephanie J. Weinstein1, Demetrius Albanes1, Philip R. Taylor1, Jarmo Virtamo3, Katherine A. McGlynn1, Neal D. Freedman1;
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; 2Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD; 3Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
Introduction: Antioxidant micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, 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 up to 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from chronic liver disease. Relative risks (RR) and 95% confidence intervals (CIs) were calculated from multivariate Cox proportional hazards models. Results: High serum β-carotene (RR=0.35, 95% CI: 0.22-0.55 for highest vs. lowest quartile; p-trend<0.0001) and retinol (RR=0.58, 95%CI: 0.39-0.85; p-trend=0.0009) were associated with reduced risk of developing liver cancer. Similarly, serum β-carotene (RR=0.47, 95% CI: 0.30-0.75; p-trend=0.001) and retinol (RR=0.55, 95% CI: 0.38-0.78; p-trend=0.0007) were inversely associated with chronic liver disease mortality. We also observed a borderline statistically significant inverse association for serum α-tocopherol and chronic liver disease mortality, (RR=0.63, 95% CI: 0.40-0.99; p-trend=0.06), but none for incident liver cancer (RR=1.06, 95%CI: 0.64-1.74; p-trend=0.77). Associations remained largely similar after removing the first 2, 5 or 10 years of follow-up. Participants with high levels of β-carotene and retinol, but not α-tocopherol, at both baseline and 3-year follow-up had a lower risk for incident liver cancer and chronic liver disease mortality than those with low levels at both times. Conclusion: Men with higher pre-diagnostic β-carotene and retinol had a lower risk of incident liver cancer and chronic liver disease mortality suggesting that higher concentrations of these micronutrients may protect against these diseases.
The following people have nothing to disclose: Gabriel Y. Lai, Stephanie J. Weinstein, Demetrius Albanes, Philip R. Taylor, Jarmo Virtamo, Katherine A. McGlynn, Neal D. Freedman