The Associations of Aspirin, Statins, and Metformin With Lung Cancer Risk and Related Mortality: A Time-Dependent Analysis of Population-Based Nationally Representative Data

Abstract

The aim of this study was to investigate the associations of aspirin, metformin, and statins with lung cancer risk and mortality using population-based nationwide cohort data. This study included a total of 732,199 participants who underwent a national health check-up from 2002 to 2003. Lung cancer incidence and mortality were identified using a registered lung cancer diagnosis code (International Classification of Diseases, 10th revision, code C34) and the Korean National Death Registry. The study participants were followed up from January 1, 2004 to December 31, 2013. Medication exposure was defined by the cumulative duration of use and cumulative defined daily dose per 2-year interval. To avoid immortal-time bias, drug exposure was inserted as a time-dependent variable in Cox analysis, which evaluated the associations of these medications with lung cancer. Metformin use had a protective association with lung cancer incidence (p's for trend 0.008) and mortality (p's for trend < 0.001) in a dose-response fashion, and these associations were prominent among participants with a metformin cumulative defined daily dose of 547.5 and above compared with patients without diabetes. Lung cancer mortality was dose-dependently reduced with the use of aspirin (p's for trends 0.046) and statin (p's for trends < 0.001). The combined use of aspirin, statins, and metformin exhibited more prominent protective associations with lung cancer risk and mortality. The use of aspirin, metformin, and statins had independent protective associations with lung cancer mortality, and metformin had an inverse association with lung cancer risk. Further studies are necessary to develop clinically applicable anticancer strategies using these drugs for the reduction of lung cancer and related mortality.