Residential greenness, air pollution, genetic predisposition and the risk of lung cancer.

Background: Growing evidence suggests that greenness is associated with multiple health outcomes, but its association with lung cancer risk remains limited and far from consistent. In particular, it is unclear whether this association varies across different types of lung cancer and whether it is influenced by factors such as genetics, air pollution, and physical activity.

Method: This prospective cohort study included 425108 participants aged 37-73 years from the UK Biobank. Residential greenness was estimated with the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) within the 500 m buffer. Cox proportional hazards regression was performed to evaluate the hazard ratios (HR) and 95 % confidence intervals (CI) of the relationship between greenness and risk of lung cancer. A genetic risk was calculated using 18 independent susceptibility loci for lung cancer. Mediation analysis was conducted to assess the indirect effects through air pollutants (including PM, PM, NO, NO) and physical activity.

Results: During a median follow-up of 14.0 years, 3814 lung cancer cases identified. An inversely linear correlation between residential greenness and incident lung cancer was found. Specifically, each interquartile range increase in NDVI and EVI within the 500 m buffer was linked to 8 % (HR 0.92, 95 % CI: 0.88, 0.96) and 9 % (HR 0.91, 95 % CI: 0.87, 0.94) decreased in lung cancer risk, respectively. Moreover, the association was particularly pronounced for adenocarcinoma (HR 0.88, 95 % CI: 0.83, 0.94 for NDVI; HR 0.87, 95 % CI: 0.82, 0.92 for EVI). Mediation analysis suggested that reductions in PM exposure and increased physical activity accounted for approximately 45 % and 1.5 % of the observed association.

Conclusion: Increased residential greenness was linearly associated with reduced risk of lung cancer, particularly adenocarcinoma, and such an association may be substantially mediated by mitigating air pollutants, especially PM and increased physical activity. The study provides promising evidence and strategy of improving greenness during urbanization to reduce the risk of lung adenocarcinoma in the context of the grimmer trend of rapidly increasing risk of adenocarcinoma.