Lung adenocarcinoma promotion by air pollutants
Authors
- W. Hill
- E.L. Lim
- C.E. Weeden
- C. Lee
- M. Augustine
- K. Chen
- F.C. Kuan
- F. Marongiu
- E.J. Evans
- D.A. Moore
- F.S. Rodrigues
- O. Pich
- B. Bakker
- H. Cha
- R. Myers
- F. van Maldegem
- J. Boumelha
- S. Veeriah
- A. Rowan
- C. Naceur-Lombardelli
- T. Karasaki
- M. Sivakumar
- S. De
- D.R. Caswell
- A. Nagano
- J.R.M. Black
- C. Martínez-Ruiz
- M.H. Ryu
- R.D. Huff
- S. Li
- M.J. Favé
- A. Magness
- A. Suárez-Bonnet
- S.L. Priestnall
- M. Lüchtenborg
- K. Lavelle
- J. Pethick
- S. Hardy
- F.E. McRonald
- M.H. Lin
- C.I. Troccoli
- M. Ghosh
- Y.E. Miller
- D.T. Merrick
- R.L. Keith
- M. Al Bakir
- C. Bailey
- M.S. Hill
- L.H. Saal
- Y. Chen
- A.M. George
- C. Abbosh
- N. Kanu
- S.H. Lee
- N. McGranahan
- C.D. Berg
- P. Sasieni
- R. Houlston
- C. Turnbull
- S. Lam
- P. Awadalla
- E. Grönroos
- J. Downward
- T. Jacks
- C. Carlsten
- I. Malanchi
- A. Hackshaw
- K. Litchfield
- J. DeGregori
- M. Jamal-Hanjani
- C. Swanton
Journal
- Nature
Citation
- Nature 616 (7955): 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 development. 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 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-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 PM(2.5) air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.