| Title: |
Lung adenocarcinoma promotion by air pollutants. |
| Authors: |
Hill, W; Lim, EL; Weeden, CE; Lee, C; Augustine, M; Chen, K; Kuan, F-C; Marongiu, F; Evans, EJ; Moore, DA; Rodrigues, FS; Pich, O; Bakker, B; Cha, H; Myers, R; van Maldegem, F; Boumelha, J; Veeriah, S; Rowan, A; Naceur-Lombardelli, C; Karasaki, T; Sivakumar, M; De, S; Caswell, DR; Nagano, A; Black, JRM; Martínez-Ruiz, C; Ryu, MH; Huff, RD; Li, S; Favé, M-J; Magness, A; Suárez-Bonnet, A; Priestnall, SL; Lüchtenborg, M; Lavelle, K; Pethick, J; Hardy, S; McRonald, FE; Lin, M-H; Troccoli, CI; Ghosh, M; Miller, YE; Merrick, DT; Keith, RL; Al Bakir, M; Bailey, C; Hill, MS; Saal, LH; Chen, Y; George, AM; Abbosh, C; Kanu, N; Lee, S-H; McGranahan, N; Berg, CD; Sasieni, P; Houlston, R; Turnbull, C; Lam, S; Awadalla, P; Grönroos, E; Downward, J; Jacks, T; Carlsten, C; Malanchi, I; Hackshaw, A; Litchfield, K; TRACERx Consortium; DeGregori, J; Jamal-Hanjani, M; Swanton, C |
| Contributors: |
Houlston, Richard; Turnbull, Clare |
| Publisher Information: |
NATURE PORTFOLIO |
| Publication Year: |
2023 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Animals; Mice; Adenocarcinoma of Lung; Air Pollutants; Air Pollution; Cell Transformation; Neoplastic; Environmental Exposure; ErbB Receptors; Lung Neoplasms; Particulate Matter; Particle Size; Cohort Studies; Macrophages; Alveolar; Alveolar Epithelial Cells |
| Subject Geographic: |
England |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; 167; application/pdf |
| Language: |
English |
| ISSN: |
1476-4687; 0028-0836 |
| Relation: |
Nature, 2023, 616 (7955), pp. 159 - 167; https://repository.icr.ac.uk/handle/internal/5854 |
| Availability: |
https://repository.icr.ac.uk/handle/internal/5854 |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.BCFB654 |
| Database: |
BASE |