Dual association of β-carotene with risk of tobacco-related cancers in a cohort of French women

Background: Intervention studies have demonstrated that, in smokers, P-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 P-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 I'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 multi-variable 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 (P-trend =.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 P-carotene intake, respectively, compared with low intake (P-trend = -09)Tests for interaction between beta-carotene intake and smoking were statistically significant (P-trend =.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 10000 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.