A Prospective Study of Serum Vitamin E and 28-Year Risk of Lung Cancer

Abstract

Background: Epidemiologic data are inconsistent regarding the vitamin E-lung cancer association, and no study to our knowledge has examined serologic changes in vitamin E status in relation to subsequent risk.

Methods: In a cohort of 22 781 male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, we ascertained 3184 lung cancer cases during up to 28 years of observation. Cox proportional hazards models examined whether higher serum alpha-tocopherol concentrations at baseline, 3 years, or the interval change were associated with lower lung cancer risk. All statistical tests were two-sided.

Results: After adjustment for age, body mass index, smoking intensity and duration, serum total cholesterol, and trial intervention group, we found lower lung cancer risk in men with high baseline alpha-tocopherol (fifth quintile [Q5] vs Q1, hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.66 to 0.87, Ptrend < .001). A similar reduction in risk was seen for serum alpha-tocopherol at 3 years (Q5 vs Q1, HR = 0.78, 95% CI = 0.67 to 0.91, Ptrend = .004). The inverse risk association appeared stronger for younger men and those who had smoked fewer years but was similar across trial intervention groups. We also found reduced risk among men not supplemented with vitamin E who had a lower serum alpha-tocopherol at baseline and greater increases in concentrations at 3 years (third tertile vs first tertile of serum alpha-tocopherol change, HR = 0.74, 95% CI = 0.59 to 0.91, P = .005).

Conclusions: Higher vitamin E status, as measured by serum alpha-tocopherol concentration, as well as repletion of a low vitamin E state, was related to decreased lung cancer risk during a 28-year period. Our findings provide evidence supporting the importance of adequate physiological vitamin E status for lung cancer risk reduction.

Figure 1.

Kaplan-Meier plot comparing cumulative incidence of lung cancer according to baseline serum alpha-tocopherol concentration quintile in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The two-sided log-rank test was used to test the differences across serum alpha-tocopherol strata.

Figure 2.

Cubic restricted spline regression for estimated relative risk of lung cancer according to baseline serum alpha-tocopherol concentration in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The reference value (9.5 mg/L; relative risk = 1.00) corresponds to the cutoff value of the first quintile of serum alpha-tocopherol concentration. The two-sided P values were derived from the likelihood ratio tests for nonlinearity and the linear relation.