Effects of ambient PM2.5 and its components on the prognosis of colorectal cancer survivors: disease progression and potential mediation pathways

Evidence continues to support the role of air pollution as a contributor to adverse outcomes in colorectal cancer (CRC); however, its effects on the mortality and disease progression transitions in CRC survivors, and the mediation pathways, remain uncertain. This retrospective cohort study enrolled 3,357 patients diagnosed with non-metastatic colorectal cancer who underwent curative surgery at Sun Yat-sen University Cancer Center between 2012 and 2017. The annual average concentrations of PM2.5 and its components were derived from the ChinaHighAirPollutants (CHAP) dataset and matched to participants based on their residential addresses. The associations between PM2.5 and its components with CRC mortality were assessed using Cox proportional hazards models. To delineate risks at different disease progression transitions, we employed multi-state models. Mediation analysis was conducted to elucidate the role of systemic inflammation and oxidative stress biomarkers in the exposure-outcome pathway. An increase in PM2.5 exposure per IQR was linked to a 35% elevated risk of CRC mortality (HR = 1.35, 95% CI: 1.18–1.54). Among the specific components analyzed, ammonium (NH₄⁺; HR = 1.51, 95% CI: 1.13–2.01) and sulfate (SO₄²⁻; HR = 1.68, 95% CI: 1.20–2.34) demonstrated significant positive associations. Stratified analyses suggested stronger associations among older patients, males, smokers, those with later-stage disease, and patients with a family history of malignancy. In multi-state models, PM2.5 exposure was consistently related to all three disease progression transitions, with HRs of 1.14 (95% CI: 1.04–1.26) for diagnosis → DFS event, 1.99 (95% CI: 1.71–2.32) for DFS event → CRC death, and 1.58 (95% CI: 1.30–1.92) for diagnosis → CRC death. Mediation analysis identified multiple inflammatory and oxidative stress biomarkers with significant indirect effects, with proportions mediated ranging from 1.7% to 8.9%. The strongest mediators were MLR (8.9%), HDL (6.6%), and PLR (3.0%). Long-term exposure to PM2.5 was associated with poorer CRC prognosis and more rapid disease progression, partly via systemic inflammation and oxidative stress. These findings support precise air quality policies and integrated survivorship strategies targeting pollution-related mortality in cancer survivors.