Air pollution and the risk of second primary lung cancer among lung cancer survivors: the prospective UK Biobank cohort study

Background Lung cancer survivors have a high risk of second primary lung cancer (SPLC). While air pollution is associated with the risk of initial primary lung cancer (IPLC), especially in never smokers, its effect on SPLC risk is unknown. Methods We identified 2439 IPLC patients from the UK Biobank, followed through 2017, linking baseline addresses to 2005–2007 annual average exposures of particulate matter (PM10) and nitrogen dioxide (NO 2 ) from the EU-wide Land Use Regression model. Associations with SPLC risk were assessed using cause-specific Cox models adjusted for co-pollutants, socioeconomic factors, smoking, and tumour characteristics. Results Of 2439 IPLC patients, 92 (3.7%) developed SPLC over 6561 person-years. The 10-year cumulative incidence of SPLC was 3.98% (3.11–4.85%). A dose-response relationship was observed between PM10 and SPLC risk, with an adjusted hazard ratio (aHR) of 6.43 (2.38–17.32) in the highest vs. lowest (aHR = 1.69 [0.68–4.19]) quintile; a co-pollutant NO 2 showed an aHR of 0.96 (0.93–0.99). The PM10 effect was pronounced in never-smoking (aHR = 2.26 [1.22–4.18]) vs. ever-smoking IPLC patients (aHR = 1.42 [1.21–1.68]) on the risk of non-small cell SPLC. Interpretation Exposure to PM10 may increase SPLC risk in lung cancer survivors, highlighting the potential value of incorporating environmental factors into SPLC surveillance to identify high-risk individuals.