Air pollution and early-onset lung cancer: from environmental carcinogenesis to early intervention strategies.

Abstract

Air pollution remains a global public health challenge, with nearly the entire global population (99%) breathing air that exceeds World Health Organization guideline limits-annual means of 5 μg/m3 for PM2.5 and 15 μg/m3 for PM10. Both household and ambient air pollution are classified as Group 1 carcinogens and contain hazardous components, including polycyclic aromatic hydrocarbons, heavy metals, and volatile organic compounds. Exposure contributes to a broad spectrum of systemic diseases and is responsible for more than 14% of global lung cancer deaths while also elevating risks for breast, gastrointestinal, and brain cancers. Mechanistically, air pollutants drive early lung carcinogenesis through intrinsic genomic instability, manifesting as DNA damage, telomere dysfunction, mitochondrial impairment, and specific mutational signatures, alongside epigenetic dysregulation. Concurrently, they foster a tumor-promoting niche via chronic inflammation mediated by CXCL13 and IL-1β and facilitate early immune evasion through activation of the PD-L1 and CD47-SIRPα axes. In addition, air pollution disrupts the respiratory-gut microbiome, reducing microbial diversity and promoting pathogenic enrichment. A range of early biomarkers-including genomic, epigenomic, inflammatory, and microbiome profiles-have been validated for preventive interventions, with multimarker combinations demonstrating improved efficacy. Multiple chemopreventive targets have also been identified to counteract oxidative stress, inflammation, and immune evasion. Looking ahead, research priorities should include exploring gene-environment interactions, clinically validating biomarkers and therapeutic targets, translating basic discoveries into clinical practice, and developing precision prevention strategies for high-risk populations. Ultimately, integrating biomarker-guided early detection with multi-target chemoprevention will be essential to reducing the global burden of air pollution-induced early-onset lung cancer.