Increased Risk of Lung Cancer in Men with Tuberculosis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

Background: Lung cancer and tuberculosis cause significant morbidity and mortality worldwide. Tuberculosis may increase lung cancer risk through substantial and prolonged pulmonary inflammation. However, prospective data on tuberculosis and lung cancer risk are limited. Methods: Our study included 29,133 Finnish male smokers followed prospectively in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-2005). Lung cancers were identified through linkage with the Finnish Cancer Registry, and hospital-treated tuberculosis cases were ascertained from the National Hospital Discharge Register. We assessed the association between tuberculosis and lung cancer risk with proportional hazards regression models, adjusting for age and cigarette smoking. Results: Forty-four lung cancer cases occurred among 273 men with tuberculosis (incidence rate 1,786 per 100,000 person-years). Tuberculosis was associated with a two-fold elevation in lung cancer risk (HR = 1.97; 95% CI = 1.46-2.65) with significant associations observed for both incident (HR = 2.05; 95% CI = 1.42-2.96) and prevalent tuberculosis (HR = 1.82; 95% CI = 1.09-3.02). Lung cancer risk was greatest in the 2-year window after tuberculosis diagnosis (HR = 5.01; 95% CI = 2.96-8.48) but remained elevated at longer latencies (HR = 1.53; 95% CI = 1.07-2.20). Though tuberculosis was associated with an increased risk of squamous cell carcinoma (HR = 3.71), adenocarcinoma (HR = 1.71), small cell carcinoma (HR = 1.72), and lung cancer of other (HR = 1.23) and unknown histologies (HR = 1.35), only the association for squamous cell carcinoma was statistically significant. Conclusions: Tuberculosis is associated with increased lung cancer risk in male smokers. Impact: Our results add to the growing body of evidence implicating chronic inflammation and pulmonary scarring in the etiology of lung cancer. Cancer Epidemiol Biomarkers Prev; 20(4); 672-8. (C) 2011 AACR.