Abstract
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 β‐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 β‐cryptoxanthin and α‐carotene intake. No clear relationship emerged with β‐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, β‐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 β‐carotene intake should be explored further. © 2006 Wiley‐Liss, Inc.