Lung adenocarcinoma promotion by air pollutants
(2023) In Nature 616(7955). p.159-167- 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 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... (More)
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.
(Less)
- author
- Hill, William ; Saal, Lao H LU ; Chen, Yilun LU ; George, Anthony M LU ; Litchfield, Kevin LU and Swanton, Charles
- author collaboration
- organization
- publishing date
- 2023-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Mice, Adenocarcinoma of Lung/chemically induced, Air Pollutants/adverse effects, Air Pollution/adverse effects, Cell Transformation, Neoplastic/chemically induced, Environmental Exposure, ErbB Receptors/genetics, Lung Neoplasms/chemically induced, Particulate Matter/adverse effects, Particle Size, Cohort Studies, Macrophages, Alveolar/drug effects, Alveolar Epithelial Cells/drug effects
- in
- Nature
- volume
- 616
- issue
- 7955
- pages
- 159 - 167
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85151530286
- pmid:37020004
- ISSN
- 0028-0836
- DOI
- 10.1038/s41586-023-05874-3
- language
- English
- LU publication?
- yes
- additional info
- © 2023. The Author(s), under exclusive licence to Springer Nature Limited.
- id
- 28256500-e9f6-4a58-88e4-67b255966841
- date added to LUP
- 2023-04-14 12:10:54
- date last changed
- 2024-04-05 18:23:38
@article{28256500-e9f6-4a58-88e4-67b255966841, abstract = {{<p>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>}}, author = {{Hill, William and Saal, Lao H and Chen, Yilun and George, Anthony M and Litchfield, Kevin and Swanton, Charles}}, issn = {{0028-0836}}, keywords = {{Animals; Mice; Adenocarcinoma of Lung/chemically induced; Air Pollutants/adverse effects; Air Pollution/adverse effects; Cell Transformation, Neoplastic/chemically induced; Environmental Exposure; ErbB Receptors/genetics; Lung Neoplasms/chemically induced; Particulate Matter/adverse effects; Particle Size; Cohort Studies; Macrophages, Alveolar/drug effects; Alveolar Epithelial Cells/drug effects}}, language = {{eng}}, number = {{7955}}, pages = {{159--167}}, publisher = {{Nature Publishing Group}}, series = {{Nature}}, title = {{Lung adenocarcinoma promotion by air pollutants}}, url = {{http://dx.doi.org/10.1038/s41586-023-05874-3}}, doi = {{10.1038/s41586-023-05874-3}}, volume = {{616}}, year = {{2023}}, }