Environmental PM 2.5 exposure associated with lung cancer in nonsmokers: a narrative review of high-risk groups, mechanisms, and implications for screening

Lung cancer remains the leading cause of cancer-related death worldwide, and an increasing proportion of cases occur in lifetime nonsmokers, particularly East Asian women. Fine particulate matter (PM2.5) in outdoor air pollution is classified as a Group 1 carcinogen and increasingly seen as an important modifiable exposure associated with lung cancer in nonsmokers. This narrative review summarizes epidemiologic and toxicological evidence linking environmental and microenvironmental PM2.5 exposures to lung cancer in nonsmokers, defined as individuals who have smoked fewer than 100 cigarettes in their lifetime. Global cohort and meta-analytic data, including dose-response findings and studies from Asian populations, are reviewed. Biological pathways linking PM2.5 to lung carcinogenesis are then examined, including oxidative stress, pulmonary inflammation, and particle-triggered cytokine and growth-factor signaling. Particular emphasis is placed on macrophage-derived interleukin-1β (IL-1β) signaling, which promotes epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. High-exposure microenvironments such as religious incense burning, residential cooking and solid-fuel use, urban transit systems (subway, bus, motorbike, and professional driving), and selected occupational settings (career and wildland firefighters, construction trades, informal e-waste recycling) are identified. These settings might contribute significantly to daily PM2.5 exposure in some individuals. Finally, future research priorities, including incorporation of cumulative PM2.5 exposure into lung cancer risk prediction models and development of cost-effective strategies for lung cancer screening in nonsmokers with high PM2.5 exposure, are presented.