Associations between alpha-tocopherol, beta-carotene, and retinol and prostate cancer survival

Abstract

Previous studies suggest that carotenoids and tocopherols (vitamin E compounds) may be inversely associated with prostate cancer risk, yet little is known about how they affect prostate cancer progression and survival. We investigated whether serum alpha-tocopherol, beta-carotene, and retinol concentrations, or the alpha-tocopherol and beta-carotene trial supplementation, affected survival of men diagnosed with prostate cancer during the alpha-Tocopherol, beta-Carotene Cancer Prevention Study, a randomized, double-blind, placebo-controlled primary prevention trial testing the effects of beta-carotene and alpha-tocopherol supplements on cancer incidence in adult male smokers in southwestern Finland (n = 29,133). Prostate cancer survival was examined using the Kaplan-Meier method with deaths from other causes treated as censoring, and using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CI) adjusted for family history of prostate cancer, age at randomization, benign prostatic hyperplasia, age and stage at diagnosis, height, body mass index, and serum cholesterol. As of April 2005, 1,891 men were diagnosed with prostate cancer and 395 died of their disease. Higher serum alpha-tocopherol at baseline was associated with improved prostate cancer survival (HR, 0.67; 95% CI, 0.45-1.00), especially among cases who had received the alpha-tocopherol intervention of the trial and who were in the highest quintile of alpha-tocopherol at baseline (HR, 0.51; 95% CI, 0.20-0.90) or at the 3-year follow-up measurement (HR, 0.26; 95% CI, 0.09-0.71). Serum beta-carotene, serum retinol, and supplemental beta-carotene had no apparent effects on survival. These findings suggest that higher alpha-tocopherol (and not beta-carotene or retinol) status increases overall prostate cancer survival. Further investigations, possibly including randomized studies, are needed to confirm this observation.

Figure 1

Fig. 1A. Prostate cancer survival by serum α-tocopherol at baseline. Kaplan-Meier plots of the probability of not dying from prostate cancer from the date of diagnosis for those in the 1^st and 2^nd quintiles of baseline serum α-tocopherol and those in the 3^rd – 5^th quintiles (≥ 10.9 mg/L). Below each graph is the total of men at risk for the same time points. Log-rank test for equality of survivor functions: Pr>chi2 = 0.03. Fig. 1B. Prostate cancer survival by serum α-tocopherol at three years. Kaplan-Meier plots of the probability of not dying from prostate cancer from the date of diagnosis for those in the 1^st and 2^nd quintiles of serum α-tocopherol at three years after entry on trial and those in the 3^rd -5^th quintiles (> 13.5 mg/L). Only men with a prostate cancer diagnosis after three years from entry on trial are included. Below each graph is the total of men at risk for the same time points. Log-rank test for equality of survivor functions: Pr>chi2 = 0.52.