| 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 |
Publication 11303
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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 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>
71 Authors
- William Hill
- Emilia L. Lim
- Clare E. Weeden
- Claudia Lee
- Marcellus Augustine
- Kezhong Chen
- Feng-Che Kuan
- Fabio Marongiu
- Edward J. Evans
- David A. Moore
- Felipe S. Rodrigues
- Oriol Pich
- Bjorn Bakker
- Hongui Cha
- Renelle Myers
- Febe van Maldegem
- Jesse Boumelha
- Selvaraju Veeriah
- Andrew Rowan
- Cristina Naceur-Lombardelli
- Takahiro Karasaki
- Monica Sivakumar
- Swapnanil De
- Deborah R. Caswell
- Ai Nagano
- James R. M. Black
- Carlos Martínez-Ruiz
- Min Hyung Ryu
- Ryan D. Huff
- Shijia Li
- Marie-Julie Favé
- Alastair Magness
- Alejandro Suárez-Bonnet
- Simon L. Priestnall
- Margreet Lüchtenborg
- Katrina Lavelle
- Joanna Pethick
- Steven Hardy
- Fiona E. McRonald
- Meng-Hung Lin
- Clara I. Troccoli
- Moumita Ghosh
- York E. Miller
- Daniel T. Merrick
- Robert L. Keith
- Maise Al Bakir
- Chris Bailey
- Mark S. Hill
- Lao H. Saal
- Yilun Chen
- Anthony M. George
- Christopher Abbosh
- Nnennaya Kanu
- Se-Hoon Lee
- Nicholas McGranahan
- Christine D. Berg
- Peter Sasieni
- Richard Houlston
- Clare Turnbull
- Stephen Lam
- Philip Awadalla
- Eva Grönroos
- Julian Downward
- Tyler Jacks
- Christopher Carlsten
- Ilaria Malanchi
- Allan Hackshaw
- Kevin Litchfield
- James DeGregori
- Mariam Jamal-Hanjani
- Charles Swanton
1 Application
| Application ID | Title |
|---|---|
| 82693 | Investigating the role of air pollution in tumour initiation across cancer types. |
Enabling scientific discoveries that improve human health