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Lung adenocarcinoma promotion by air pollutants

Item Type:Article
Title:Lung adenocarcinoma promotion by air pollutants
Creators Name:Hill, W. and Lim, E.L. and Weeden, C.E. and Lee, C. and Augustine, M. and Chen, K. and Kuan, F.C. and Marongiu, F. and Evans, E.J. and Moore, D.A. and Rodrigues, F.S. and Pich, O. and Bakker, B. and Cha, H. and Myers, R. and van Maldegem, F. and Boumelha, J. and Veeriah, S. and Rowan, A. and Naceur-Lombardelli, C. and Karasaki, T. and Sivakumar, M. and De, S. and Caswell, D.R. and Nagano, A. and Black, J.R.M. and Martínez-Ruiz, C. and Ryu, M.H. and Huff, R.D. and Li, S. and Favé, M.J. and Magness, A. and Suárez-Bonnet, A. and Priestnall, S.L. and Lüchtenborg, M. and Lavelle, K. and Pethick, J. and Hardy, S. and McRonald, F.E. and Lin, M.H. and Troccoli, C.I. and Ghosh, M. and Miller, Y.E. and Merrick, D.T. and Keith, R.L. and Al Bakir, M. and Bailey, C. and Hill, M.S. and Saal, L.H. and Chen, Y. and George, A.M. and Abbosh, C. and Kanu, N. and Lee, S.H. and McGranahan, N. and Berg, C.D. and Sasieni, P. and Houlston, R. and Turnbull, C. and Lam, S. and Awadalla, P. and Grönroos, E. and Downward, J. and Jacks, T. and Carlsten, C. and Malanchi, I. and Hackshaw, A. and Litchfield, K. and DeGregori, J. and Jamal-Hanjani, M. and Swanton, C.
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.
Keywords:Cancer Genomics, Non-Small-Cell Lung Cancer, Preclinical Research, Risk Factors, Animals, Mice
Publisher:Nature Publishing Group
Page Range:159-167
Date:6 April 2023
Additional Information:Tom Kaufmann is a member of TRACERx Consortium
Official Publication:https://doi.org/10.1038/s41586-023-05874-3
PubMed:View item in PubMed

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