Title: | Lung adenocarcinoma promotion by air pollutants |
Journal: | Nature |
Published: | 5 Apr 2023 |
Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37020004/ |
DOI: | https://doi.org/10.1038/s41586-023-05874-3 |
URL: | https://europepmc.org/articles/pmc7614604?pdf=render |
Title: | Lung adenocarcinoma promotion by air pollutants |
Journal: | Nature |
Published: | 5 Apr 2023 |
Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37020004/ |
DOI: | https://doi.org/10.1038/s41586-023-05874-3 |
URL: | https://europepmc.org/articles/pmc7614604?pdf=render |
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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 development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), 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 PM2.5 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-1β. 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 PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.</p>
Application ID | Title |
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82693 | Investigating the role of air pollution in tumour initiation across cancer types. |
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