Digitalis use and lung cancer risk by histological type in men

Lung cancer risk and tumor characteristics differ between sexes. Estrogen has been suggested to counteract lung cancer development. We aimed to test the hypothesis that digitalis use decreases lung cancer risk due to its estrogenic and other anticancer properties in men. This was a nationwide Swedish population‐based cohort study between July 1, 2005 and December 31, 2013. Data on the use of digitalis and organic nitrates in all male individuals were derived from the Swedish Prescribed Drug Registry. New lung cancer diagnoses among cohort participants were identified from the Swedish Cancer Registry. Cox proportional hazards regression was employed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of lung cancer in digitalis users (exposed participants) compared to users of organic nitrates without digitalis medication (unexposed participants). The study cohort contained 74,437 digitalis users and 297,301 organic nitrates users. Long‐term use (≥2 years) of digitalis was associated with decreased HRs of total lung cancer (HR 0.55, 95% CI 0.39–0.79) and squamous cell carcinoma (HR 0.40, 95% CI 0.19–0.87). This large and population‐based study suggests decreased risks of lung cancer overall and squamous cell carcinoma associated with long‐term use of digitalis in men. What's new? While estrogens are thought to play a role in lung cancer, their effects remain unclear. Epidemiological studies examining estrogen and lung cancer development have centered on women, and the results have been inconclusive. Here, to better understand the role of estrogenic exposure in lung carcinogenesis, the authors assembled a large cohort of men and examined associations between lung cancer and use of digitalis, an estrogen‐mimicking compound. Digitalis use for two or more years was associated with a reduced risk of lung cancer overall. The inverse association was especially strong for squamous cell carcinoma of the lung.