β-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine

Introduction: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated that beta-carotene supplementation increases lung cancer incidence in smokers. Further, cigarettes with higher tar and nicotine content are associated with a higher risk of lung cancer. However, no studies have examined whether the increased risk associated with beta-carotene supplementation in smokers varies by the tar or nicotine content of cigarettes. Methods: The ATBC Study was a randomized, double-blind intervention trial conducted in southwest Finland. A total of 29 133 male smokers, aged 50-69 years, were enrolled and randomly assigned to one of four groups (alpha-tocopherol, beta-carotene, both, or placebo). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by beta-carotene trial assignment stratified by a priori categories of cigarette tar and nicotine content. Results: The beta-carotene supplementation group had significantly higher risk of developing lung cancer in all categories of tar content (yes vs. no beta-carotene supplementation-ultralight cigarettes [<= 7 mg tar]: HR = 1.31, 95% CI = 0.91 to 1.89; nonfiltered cigarettes [>= 21 mg tar]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .91). Similarly, there was no interaction with nicotine content (yes vs. no beta-carotene supplementation-ventilated cigarettes [<= 0.8 mu g nicotine]: HR = 1.23, 95% CI = 0.98 to 1.54; nonfiltered cigarettes [>= 1.3 mu g nicotine]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .83). Conclusion: These findings support the conclusion that supplementation with beta-carotene increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers should continue to avoid beta-carotene supplementation.