Breathing carcinogens: PM_2.5 air pollution and lung cancer in never-smokers, a narrative review

Background and Objective: Lung cancer in never-smokers (LCINS) disproportionately affects women and younger individuals, and its incidence has increased over recent decades. Environmental respiratory hazards, such as particulate matter ≤2.5 µm (PM_2.5), are associated with lung cancer incidence and mortality, but the mechanisms by which PM_2.5 increases lung cancer susceptibility remain incompletely understood. This review summarizes the current evidence linking PM_2.5 exposure to LCINS and identifies priorities for future research.

Methods: A narrative review was conducted using PubMed/MEDLINE to identify English-language studies published from 2000 through May 2026 using combinations of the terms “PM_2.5”, “fine particulate matter”, “air pollution”, “lung cancer”, “never-smokers”, “environmental respiratory hazards”, “genomic alterations”, and “tumor microenvironment”. Additional relevant studies were identified through manual review of the reference lists of included articles. Studies were selected based on their relevance to the epidemiology, biological mechanisms, genomic and immune landscape, and clinical implications of PM_2.5-associated LCINS, with emphasis on original investigations, high-quality reviews, and landmark publications.

Key Content and Findings: PM_2.5 exposure promotes inflammatory signaling, metabolic reprogramming, and tumor progression. Emerging evidence suggests that PM_2.5 functions primarily as a tumor promoter rather than a direct mutagen and is associated with genomic and epigenetic alterations, more advanced disease, and worse survival following lung cancer diagnosis and surgical resection. LCINS also exhibits distinct molecular and immunologic characteristics with important implications for screening, molecular profiling, and targeted therapies.

Conclusions: PM_2.5 is an increasingly recognized contributor to lung carcinogenesis in never-smokers. Improved understanding of the biologic mechanisms linking environmental respiratory hazards to LCINS may inform future screening strategies, precision oncology approaches, and novel therapeutic targets for this growing and understudied patient population.