Lung adenocarcinoma promotion by air pollutants.
Loading...
Embargo End Date
ICR Authors
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
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
Document Type
Journal Article
Date
2023-04-06
Date Accepted
2023-02-21
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.
Citation
Nature, 2023, 616 (7955), pp. 159 - 167
Source Title
Nature
Publisher
NATURE PORTFOLIO
ISSN
0028-0836
eISSN
1476-4687
1476-4687
1476-4687
Collections
Research Team
Cancer Genomics
Lung Cancer Group
Lung Cancer Group