β-carotene Supplementation and Lung Cancer Incidence in the ATBC Study: the Role of Tar and Nicotine.

Introduction The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated that β-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 β-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. 29,133 male smokers, aged 50-69 years were enrolled and randomly assigned to one of four groups (α-tocopherol, β-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 β-carotene trial assignment stratified by a priori categories of cigarette tar and nicotine content. Results The β-carotene supplementation group had significantly higher risk of developing lung cancer in all categories of tar content [yes versus no β-carotene supplementation - ultra-light cigarettes (≤7 mg tar): HR=1.31 95% CI=0.91-1.89; non-filtered cigarettes (≥21 mg tar): HR=1.22 95% CI=0.91-1.64; p for interaction=0.91]. Similarly, there was no interaction with nicotine content [yes versus no β-carotene supplementation - ventilated cigarettes (≤0.8 µg nicotine) HR=1.23, 95% CI=0.98-1.54; non-filtered cigarettes (≥1.3 µg nicotine): HR=1.22, 95% CI=0.91-1.64; p for interaction=0.83]. Conclusion These findings support the conclusion that supplementation with β-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 β-carotene supplementation. Implications Previous studies demonstrated that β-carotene supplementation increases risk of lung cancer in smokers. This study moves the field forward by examining the potential for modification of risk of lung cancer with different levels of tar and nicotine in cigarettes smoked, as interaction with carcinogens in these components of cigarette smoke are hypothesized to be the mechanism by which β-carotene increases risk.  Our study provides evidence that the increased risk of lung cancer in smokers who take β-carotene supplements is not dependent upon the tar or nicotine level of cigarettes smoked and suggests that all smokers should continue to avoid β-carotene supplementation.