The link between long-term exposure to tropospheric ozone (O3) and risk of lung cancer mortality remains uncertain. We aimed to provide new insights into the association between long-term O3 exposure and lung cancer mortality in Korea. A nested case-control study was conducted within a cancer-free cohort of 1,731,513 individuals who underwent health screenings provided by the National Health Insurance Service in 2006–2007. A total of 7133 lung cancer deaths that occurred from January 1, 2012, to December 31, 2021, were matched to 28,532 controls at a 1:4 ratio based on propensity scores. Daily 24-h and 8-h maximum O3 concentrations, averaged year-round and during the warm season from 2006 to 2010, were estimated for participants based on their residential addresses using the Community Multiscale Air Quality model. O3 concentrations rise during the daytime, also exhibiting seasonal variations, with the highest levels occurring in the warm season. Elevated risk of lung cancer mortality was observed among participants in the highest quartile of O3 exposure compared with those in the lowest quartile, yielding odds ratios ranging from 1.15 to 1.27. However, when exposure to particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) was further adjusted for, the adverse risk of long-term O3 exposure was attenuated, even tending to be protective. Notably, participants with both high O3 and high PM2.5 exposures had an increased risk of lung cancer mortality. Furthermore, regional differences were observed, with a significantly higher risk in rural areas. Findings of this study suggest that long-term exposure to O3, especially in combination with PM2.5 exposure, is associated with an excess risk of lung cancer mortality, underscoring the importance of addressing the O3 and PM2.5 interaction in lung cancer prevention.
