Serum α-Tocopherol and γ-Tocopherol Concentrations and Prostate Cancer Risk in the PLCO Screening Trial: A Nested Case-Control Study

PLoS ONE

Jul 2012

DOI: 10.1371/journal.pone.0040204

Citations:38

Influential Citations:1

Observational Studies (Human)

Enhanced Details

Methods

Population: men aged 55-74 from the PLCO Screening Trial (screening arm). Design: nested case-control study within a prospective cohort. Participants: 680 prostate cancer cases and 824 controls; cases were non-Hispanic white men diagnosed with adenocarcinoma of the prostate at least 1 year after blood draw; controls selected by incidence-density sampling and frequency-matched on age (5-year intervals), time since initial screening, and year of blood collection. Baseline non-fasting blood samples were used to measure serum a-tocopherol and c-tocopherol. Analysis used conditional logistic regression to estimate odds ratios for tocopherol quintiles; stratified analyses by disease stage and smoking status were performed.

Results

Higher serum a-tocopherol is associated with a reduced risk of prostate cancer, strongest among current smokers and recent quitters; highest vs lowest quintile OR = 0.63 (95% CI 0.44-0.92; p-trend = 0.05). No clear association for c-tocopherol (OR for highest vs lowest quintile 1.35; 95% CI 0.92-1.97; p-trend = 0.41). A stronger inverse pattern was observed for aggressive disease; a post-hoc analysis suggested the combination of high a-tocopherol and low c-tocopherol confers the lowest risk (OR ≈ 0.53). Excluding supplement users attenuated the a-tocopherol effect but the smoking-related pattern persisted. Authors conclude that higher a-tocopherol status may reduce prostate cancer risk, particularly among smokers, while randomized trials have not consistently shown benefit; further work is needed to understand mechanisms, stage-specific effects, and smoking interactions.

Limitations

Observational, nested case-control design limits causal inferences; potential residual confounding; baseline blood samples were non-fasting with a single measurement; follow-up duration ~8 years; relatively few current smokers in some subgroups; substantial supplement use may influence tocopherol levels and associations; study population limited to men aged 55-74 in the PLCO trial, limiting generalizability.

Abstract

Background Vitamin E compounds exhibit prostate cancer preventive properties experimentally, but serologic investigations of tocopherols, and randomized controlled trials of supplementation in particular, have been inconsistent. Many studies suggest protective effects among smokers and for aggressive prostate cancer, however. Methods We conducted a nested case-control study of serum α-tocopherol and γ-tocopherol and prostate cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, with 680 prostate cancer cases and 824 frequency-matched controls. Multivariate-adjusted, conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for tocopherol quintiles. Results Serum α-tocopherol and γ-tocopherol were inversely correlated (r = −0.24, p<0.0001). Higher serum α-tocopherol was associated with significantly lower prostate cancer risk (OR for the highest vs. lowest quintile = 0.63, 95% CI 0.44–0.92, p-trend 0.05). By contrast, risk was non-significantly elevated among men with higher γ-tocopherol concentrations (OR for the highest vs. lowest quintile = 1.35, 95% CI 0.92–1.97, p-trend 0.41). The inverse association between prostate cancer and α-tocopherol was restricted to current and recently former smokers, but was only slightly stronger for aggressive disease. By contrast, the increased risk for higher γ-tocopherol was more pronounced for less aggressive cancers. Conclusions Our findings indicate higher α-tocopherol status is associated with decreased risk of developing prostate cancer, particularly among smokers. Although two recent controlled trials did not substantiate an earlier finding of lower prostate cancer incidence and mortality in response to supplementation with a relatively low dose of α-tocopherol, higher α-tocopherol status may be beneficial with respect to prostate cancer risk among smokers. Determining what stage of prostate cancer development is impacted by vitamin E, the underlying mechanisms, and how smoking modifies the association, is needed for a more complete understanding of the vitamin E-prostate cancer relation. show less