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Publication : Lung adenocarcinoma promotion by air pollutants.

First Author  Hill W Year  2023
Journal  Nature Volume  616
Issue  7955 Pages  159-167
PubMed ID  37020004 Mgi Jnum  J:339992
Mgi Id  MGI:7525547 Doi  10.1038/s41586-023-05874-3
Citation  Hill W, et al. (2023) Lung adenocarcinoma promotion by air pollutants. Nature 616(7955):159-167
abstractText  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.
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