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

Abstract

Background: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 (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 β-carotene and retinol levels were associated with less liver cancer (β-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 (β-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 β-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 β-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.

The Association between Dietary Vitamin A and Carotenes and the Risk of Primary Liver Cancer: A Case–Control Study

“…Similar favorable associations were observed in a large prospective study (the ATBC study) in 208 PLC cases from 29,046 men with baseline serum retinol/beta-carotene data, followed up for 24-years [10]. A few retrospective case–control studies also showed beneficial associations between liver cancer and beta-carotene and retinol levels in blood [10,11,12,13,14] and for the relevant dietary markers [11]. However, null or even opposite results were observed in some studies.…”

“…In a Shanghai cohort study [9], higher prediagnostic serum levels of retinol were related to a decreased risk of hepatocellular carcinoma (HCC). Similar favorable associations were observed in a large prospective study (the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study [10]) and in some case–control studies [11,12,13,14] between liver cancer beta-carotene and retinol levels in blood [10,11,12,13,14] and dietary sources [11]. However, null or even opposite results were observed in some studies.…”

“…The possible reasons for the between-study heterogeneity may be due to the variations in study design, exposure makers, exposure dosage, and covariate adjustments. Favorable associations tended to be more frequently observed in case–control [11,12,13,14] (vs. cohort [15]) studies, in observational [10,11,12,13,14] (vs. interventional [16,17,18]) studies, in those using circulating [10,11,12,13,14] (vs. dietary intake [11,15]), and with low to moderate [15,28] (vs. high [17,18]) exposure or interventional dosages. Typically, blood measurements of retinol or beta-carotene had much higher precision in the determination of the internal doses than their dietary assessments, due to much smaller random error.…”

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

“…60 However, no link between serum α-T levels and risk of liver cancer was found in a follow-up of the ATBC trial. 61 The prospective Vitamins and Lifestyle study found serum α-T levels had no connection with urothelial cancer rates. 62 A recent meta-analysis also found no relationship between non-Hodgkin's Lymphoma and VE intake.…”

“…Also, in meta‐analyses, inverse associations were observed between serum levels of α‐T and breast cancer risk by Hu et al 80 as well as renal cancer by Shang et al 81 and Shen et al 82 In the combined Shanghai Women's and Men's Health Studies, dietary VE intake (including supplements) was inversely associated with liver cancer risk 60 . However, no link between serum α‐T levels and risk of liver cancer was found in a follow‐up of the ATBC trial 61 . The prospective Vitamins and Lifestyle study found serum α‐T levels had no connection with urothelial cancer rates 62 .…”