Long-Term Fine Particulate Matter Exposure on Lung Cancer Incidence and Mortality in Chinese Nonsmokers

Rationale: The association between fine particulate matter (PM2.5) and lung cancer incidence in non-smokers (LCINS) remains inconsistent. Objectives: To investigate the association between long-term PM2.5 exposure and LCINS in a Chinese population and to assess the modifying effect of genetic factors. Methods: Time-dependent Cox proportional hazard models were employed to evaluate the hazard ratios (HR) and 95% confidence interval (CI) of PM2.5 with LCINS risk and LCINS-related mortality. The polygenic risk score (PRS) was constructed to further explore the interactions between genetic risk and PM2.5 exposure. Additionally, the population attributable fraction (PAF) of PM2.5 to lung cancer risk and mortality was calculated. Measurements and Main Results: The results demonstrated significant associations between PM2.5 exposure and LCINS incidence (HR: 1.10, 95% confidence interval [CI]: 1.04-1.17, per 10 µg/m3) and mortality (HR: 1.17, 95% CI: 1.08-1.27, per 10 µg/m3). Compared to the lowest-risk group, individuals exposed to the high PM2.5 level (≥50.9 µg/m3) and high genetic risk (top 30%) exhibited the highest LCINS incidence (HR: 2.01, 95% CI: 1.39-2.87) and mortality (HR: 2.30, 95% CI: 1.38-3.82). A significant additive interaction between PM2.5 and genetic risk on LCINS incidence was observed. Approximately 33.6% of LCINS cases and 48.5% of LCINS-related deaths in China could be prevented if PM2.5 concentrations were reduced to meet WHO guidelines. Conclusion: Long-term exposure to outdoor PM2.5 increases LCINS risk and LCINS-related mortality, especially in populations with high genetic risk. Strengthening air pollution control measures in China has the potential to significantly reduce the burden of LCINS.