Prospective study of vitamins C, E, and A and carotenoids and risk of oral premalignant lesions in men.

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of beta-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p(trend) = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for beta-cryptoxanthin and alpha-carotene intake. No clear relationship emerged with beta-carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06-3.19), particularly among current smokers and with supplemental intake (current-smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28-7.34, p(trend) = 0.01). For current smokers, beta-carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or beta-carotene intake should be explored further.