Long-term exposure to fine particulate matter constituents and lung cancer risk in Chinese never-smokers

Although long-term exposure to fine particulate matter (PM_2.5) has been linked to lung cancer incidence in never-smokers (LCINS), evidence for PM_2.5 constituents remains limited. This study included 262,785 never-smokers from the China Kadoorie Biobank, among whom 2646 LCINS cases were identified. Annual average concentrations of PM_2.5 and its major constituents during 2004-2018 were obtained from the ChinaHighAirPollutants database. Time-dependent Cox proportional hazards models estimated constituent associations with LCINS incidence, and Quantile-based g-computation assessed the importance of each constituent. The polygenic risk score (PRS) was constructed to explore the multiplicative and additive interactions between genetic risk and pollutant constituents. Per interquartile range increase, exposure to nitrate (NO₃^-), ammonium (NH₄⁺), and chloride (Cl^-) was associated with higher LCINS risk, with hazard ratios (HRs) of 1.35 (95% confidence interval (CI), 1.23-1.48), 1.22 (95% CI, 1.13-1.31), and 1.20 (95% CI, 1.12-1.28), respectively. Mixture analyses consistently identified NO₃^- and NH₄⁺ as the largest positive contributors to the overall PM_2.5-related risk, with an overall mixture HR of 1.13 (95% CI, 1.07-1.19). Significant additive and multiplicative interactions between NO₃^- exposure and PRS were observed. These findings suggest that long-term exposure to specific PM_2.5 constituents, particularly NO₃^-, was associated with higher LCINS risk, especially among genetically susceptible individuals.