Lung cancer risk associated with pulmonary tuberculosis and inflammatory lesions in the lungs

Abstract

Background. The inflammatory response induced by tuberculosis, scarring, and granulomas may increase the risk for lung cancer. Methods. (I) SEER-Medicare linked database was used to examine the association of lung cancer and history of tuberculosis among persons aged 65 and older. We included lung cancer cases from SEER registries and frequency-matched population-based controls. Medicare claims data were used to ascertain of tuberculosis. We analyzed the association between case/control status and tuberculosis using logistic regression models adjusting for sex, age, race, SEER registry, and year of selection. To explore the possibility of confounding by smoking, we also assessed the association with larynx and bladder cancers, because these two types of cancer are known to be associated with smoking but not tuberculosis. (II) Data from the PLCO cancer screening trial were examined to test the association between lung cancer and baseline chest radiographic (CXR) diagnosis of granulomas and scarring. The screening cohort received a baseline CXR and completed a study questionnaire. We used multivariable Cox proportional hazards models to estimate the HRs adjusted for age at randomization, sex, race and cumulative tobacco smoking. Results. (I) We identified 107,389 lung cancer cases and the same number of controls. Odds of having tuberculosis within the previous 17 years were 4.2 times higher among cases than controls (95% CI 3.5-5.1) adjusted for confounders. The association was stronger when history of tuberculosis was defined in terms of inpatient claims (OR 4.7) compared to outpatient claims (OR 3.8). The association was strongest in the year preceding lung cancer diagnosis (OR 10.4), but was still significant in the 1-10 year period prior (OR 2.5). We also found increased odds of having tuberculosis among larynx cancer cases (OR 3.6), but not among bladder cancer cases (OR 1.2), compared to controls. (II) 809 lung cancers were identified following baseline CXRs. Increased lung cancer risk was associated with the presence of scars (HR 1.5, 95% CI 1.2-1.8) but not granulomas (HR 1.1, 95% CI 0.9-1.4). The findings were consistent across time (1-10 years). Conclusion. The possible etiologic associations between lung cancer and pulmonary damage induced by tuberculosis or other scarring conditions may be mediated through chronic inflammation.