Lung adenocarcinoma promotion by air pollutants
Details
Publication Year 2023,Volume 616,Issue #7955,Page 159-167
Journal Title
Nature
Publication Type
Research article
Abstract
A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development(1). Here we propose that environmental particulate matter measuring </=2.5 mum (PM(2.5)), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM(2.5) levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1beta. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM(2.5) air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.
Keywords
Animals; Mice; *Adenocarcinoma of Lung/chemically induced/genetics; *Air Pollutants/adverse effects/analysis; *Air Pollution/adverse effects/analysis; *Cell Transformation, Neoplastic/chemically induced/drug effects/genetics; Environmental Exposure; ErbB Receptors/genetics; *Lung Neoplasms/chemically induced/genetics; Particulate Matter/adverse effects/analysis; Particle Size; Cohort Studies; Macrophages, Alveolar/drug effects; Alveolar Epithelial Cells/drug effects/pathology
Department(s)
Laboratory Research
PubMed ID
37020004
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