Abstract Background: Globally, lung cancer is the most common cancer and the leading cause of cancer death. Early observational studies reported a protective association between intake of β-carotene rich vegetables and lung cancer risk, which led to interest in β-carotene supplementation as a potential chemopreventive strategy, particularly in high-risk populations such as cigarette smokers. A large randomized controlled trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, demonstrated that β-carotene supplementation increased lung cancer incidence by 18% in smokers, and led to an 8% excess in overall mortality. It is also well-documented that cigarettes with higher (versus lower) tar and nicotine content are associated with a higher risk of lung cancer. To our knowledge, however, no studies have examined whether the increased risk associated with β-carotene supplementation in smokers varies by cigarette tar or nicotine content. Methods: The ATBC Study was a randomized, double-blind vitamin supplementation trial conducted among 29,133 male smokers in southwest Finland. Participants were randomly assigned to one of four groups in a 2x2 factorial design (α-tocopherol alone, β-carotene alone, both supplements, or placebo). A detailed smoking history was collected at baseline, including brands of cigarettes smoked (for which machine measured tar and nicotine content was available). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by trial B-carotene assignment stratified by a priori categories of cigarette tar (ultra-light ≤7 mg, light 8-14 mg, medium/regular 15-20 mg, high/non-filtered/self-made >20 mg) and nicotine content (ventilated filtered ≤0.8 µg, unventilated filtered 0.8-1.3 µg, non-filtered >1.3 µg). Statistical interaction was estimated using the likelihood ratio test. Results: The β-carotene supplemented arm had a statistically significantly higher risk of developing lung cancer in all categories of tar content [yes vs. no β-carotene supplementation - ultra-light: HR=1.31 95% CI=0.91-1.89; non-filtered: HR=1.22 95% CI=0.91-1.64; p-interaction=0.91]. Similarly, there was no apparent interaction with cigarette nicotine content [yes vs. no β-carotene supplementation - ventilated cigarettes: HR=1.23, 95% CI=0.98-1.54; non-filtered cigarettes: HR=1.22, 95% CI=0.91-1.64; p-interaction=0.83]. Conclusion: These findings indicate that supplementation with β-carotene increases lung cancer incidence in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers, regardless of the type of cigarette smoked, should continue to avoid β-carotene supplementation. Citation Format: Pooja Middha, Stephanie J. Weinstein, Satu Männistö, Demetrius Albanes, Alison M. Mondul. B-carotene supplementation and lung cancer risk in the ATBC Study: the role of tar and nicotine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2289. doi:10.1158/1538-7445.AM2017-2289
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Jul 26, 2022
Wayne Hall 
Open Access
