Urban residential greenness and cancer mortality: Evaluating the causal mediation role of air pollution in a large cohort

Evidence linking greenness to all-site and site-specific cancers remains limited, and the complex role of air pollution in this pathway is unclear. We aimed to fill these gaps by using a large cohort in southern China. A total of 654,115 individuals were recruited from 2009 to 2015 and followed-up until December 2020. We calculated the normalized difference vegetation index (NDVI) in a 500-m buffer around the participants’ residences to represent the greenness exposure. Cox proportional-hazards models were used to evaluate the impact of greenness on the risk of all-site and site-specific cancer mortality. Additionally, we assessed both the mediation and interaction roles of air pollution (i.e., PM_2.5, PM₁₀, and NO₂) in the greenness–cancer association through a causal mediation analysis using a four-way decomposition method. Among the 577,643 participants, 10,088 cancer deaths were recorded. We found a 10% (95% CI: 5–16%) reduction in all-site cancer mortality when the NDVI increased from the lowest to the highest quartile. When stratified by cancer type, our estimates suggested 18% (95% CI: 8–27%) and 51% (95% CI: 16–71%) reductions in mortality due to respiratory system cancer and brain and nervous system cancer, respectively. For the above protective effect, a large proportion could be explained by the mediation (all-site cancer: 1.0–27.7%; respiratory system cancer: 1.2–32.3%; brain and nervous system cancer: 3.6–109.1%) and negative interaction (all-site cancer: 2.1–25.7%; respiratory system cancer: 2.0–25.7%; brain and nervous system cancer: not significant) effects of air pollution. We found that particulate matter (i.e., PM_2.5 and PM₁₀) had a stronger causal mediation effect (25.0–109.1%) than NO₂ (1.0–3.6%), while NO₂ had a stronger interaction effect (25.7%) than particulate matter (2.0–2.8%). In summary, greenness was significantly beneficial in reducing the mortality of all-site, respiratory system, and brain and nervous system cancer in southern China, with the impact being modulated and mediated by air pollution.