Dual association of beta-carotene with risk of tobacco-related cancers in a cohort of french women.

Comment in:
J Natl Cancer Inst. 2005 Sep 21;97(18):1319-21.

BACKGROUND: Intervention studies have demonstrated that, in smokers, beta-carotene supplements had a deleterious effect on risk of lung cancer and may have a deleterious effect on digestive cancers as well. We investigated a potential interaction between beta-carotene intake and smoking on the risk of tobacco-related cancers in women. METHODS: A total of 59,910 women from the French Etude Epidemiologique de Femmes de la Mutuelle Generale de l’Education Nationale (E3N) prospective investigation were studied from 1994. After a median follow-up of 7.4 years, 700 women had developed cancers known to be associated with smoking. Diet, supplement use, and smoking status at baseline were assessed by self-report. beta-carotene intake was classified into four groups: first (low intake), second, and third tertiles of dietary intake, and use of supplements (high intake). Unadjusted and multivariable Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (CIs) for cancer risk. All statistical tests were two-sided. RESULTS: Among never smokers, multivariable hazard ratios of all smoking-related cancers were 0.72 (95% CI = 0.57 to 0.92), 0.80 (95% CI = 0.64 to 1.01), and 0.44 (95% CI = 0.18 to 1.07) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .03). Among ever smokers, multivariable hazard ratios were 1.43 (95% CI = 1.05 to 1.96), 1.20 (95% CI = 0.86 to 1.67), and 2.14 (95% CI = 1.16 to 3.97) for the second and third tertiles of dietary intake, and high beta-carotene intake, respectively, compared with low intake (Ptrend = .09). Tests for interaction between beta-carotene intake and smoking were statistically significant (Ptrend =.017). In this population, the absolute rates over 10 years in those with low and high beta-carotene intake were 181.8 and 81.7 cases per 10,000 women in never smokers and 174.0 and 368.3 cases per 10,000 women in ever smokers. CONCLUSIONS: beta-carotene intake was inversely associated with risk of tobacco-related cancers among nonsmokers with a statistically significant dose-dependent relationship, whereas high beta-carotene intake was directly associated with risk among smokers.