Association of serum α-tocopherol, ß-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 α-tocopherol, ß-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 ß-carotene and retinol levels were associated with less liver cancer (ß-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 (ß-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-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 ß-carotene and retinol, but not α-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 ß-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.

Effects of α-tocopherol and ß-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

BACKGROUND: Recent data suggest the possible benefits of α-tocopherol and ß-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. METHODS: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) ß-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. RESULTS: Supplemental α-tocopherol, ß-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. CONCLUSIONS: Long-term supplemental α-tocopherol or ß-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

BACKGROUND: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. METHODS: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. RESULTS: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. CONCLUSION: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Low serum and red blood cell folate are moderately, but nonsignificantly associated with increased risk of invasive cervical cancer in U.S. women.

Previous observational epidemiologic studies of folate and cervical cancer, as well as folate supplementation trials for cervical dysplasia, have produced mixed results. We examined the relationship between serum and RBC folate and incident invasive cervical cancer in a large, multicenter, community-based case-control study. Detailed in-person interviews were conducted, and blood was drawn at least 6 mo after completion of cancer treatment from 51% of cases and 68% of controls who were interviewed. Blood folate was measured with both microbiologic and radiobinding assays. Included in the final analyses were 183 cases and 540 controls. Logistic regression was used to control for all accepted risk factors, including age, sexual behavior, smoking, oral contraceptive use, Papanicolaou smear history and human papillomavirus (HPV)-16 serology. For all four folate measures, the geometric mean in cases was lower than in controls (e.g., 11.6 vs. 13.0 nmol/L, P < 0.01 for the serum radiobinding assay). Folate measures using microbiologic and radiobinding assays were correlated (serum: r = 0.90; RBC: r = 0.77). For serum folate, multivariate-adjusted odds ratios (OR) in the lowest vs. highest quartile were 1.3 [95% confidence interval (CI) = 0.8--2.9] and 1.6 (0.9--2.9), using the microbiologic and radiobinding assays, respectively. For RBC folate, comparable OR were 1.2 (0.6--2.2) and 1.5 (0.8--2.7). Similar risks were obtained when restricting analyses to subjects with a history of HPV infection. Thus, low serum and RBC folate were each moderately, but nonsignificantly, associated with increased invasive cervical cancer risk. These findings support a role for one-carbon metabolism in the etiology of cervical cancer.