dc.contributor.author | Hill, W | |
dc.contributor.author | Lim, EL | |
dc.contributor.author | Weeden, CE | |
dc.contributor.author | Lee, C | |
dc.contributor.author | Augustine, M | |
dc.contributor.author | Chen, K | |
dc.contributor.author | Kuan, F-C | |
dc.contributor.author | Marongiu, F | |
dc.contributor.author | Evans, EJ | |
dc.contributor.author | Moore, DA | |
dc.contributor.author | Rodrigues, FS | |
dc.contributor.author | Pich, O | |
dc.contributor.author | Bakker, B | |
dc.contributor.author | Cha, H | |
dc.contributor.author | Myers, R | |
dc.contributor.author | van Maldegem, F | |
dc.contributor.author | Boumelha, J | |
dc.contributor.author | Veeriah, S | |
dc.contributor.author | Rowan, A | |
dc.contributor.author | Naceur-Lombardelli, C | |
dc.contributor.author | Karasaki, T | |
dc.contributor.author | Sivakumar, M | |
dc.contributor.author | De, S | |
dc.contributor.author | Caswell, DR | |
dc.contributor.author | Nagano, A | |
dc.contributor.author | Black, JRM | |
dc.contributor.author | Martínez-Ruiz, C | |
dc.contributor.author | Ryu, MH | |
dc.contributor.author | Huff, RD | |
dc.contributor.author | Li, S | |
dc.contributor.author | Favé, M-J | |
dc.contributor.author | Magness, A | |
dc.contributor.author | Suárez-Bonnet, A | |
dc.contributor.author | Priestnall, SL | |
dc.contributor.author | Lüchtenborg, M | |
dc.contributor.author | Lavelle, K | |
dc.contributor.author | Pethick, J | |
dc.contributor.author | Hardy, S | |
dc.contributor.author | McRonald, FE | |
dc.contributor.author | Lin, M-H | |
dc.contributor.author | Troccoli, CI | |
dc.contributor.author | Ghosh, M | |
dc.contributor.author | Miller, YE | |
dc.contributor.author | Merrick, DT | |
dc.contributor.author | Keith, RL | |
dc.contributor.author | Al Bakir, M | |
dc.contributor.author | Bailey, C | |
dc.contributor.author | Hill, MS | |
dc.contributor.author | Saal, LH | |
dc.contributor.author | Chen, Y | |
dc.contributor.author | George, AM | |
dc.contributor.author | Abbosh, C | |
dc.contributor.author | Kanu, N | |
dc.contributor.author | Lee, S-H | |
dc.contributor.author | McGranahan, N | |
dc.contributor.author | Berg, CD | |
dc.contributor.author | Sasieni, P | |
dc.contributor.author | Houlston, R | |
dc.contributor.author | Turnbull, C | |
dc.contributor.author | Lam, S | |
dc.contributor.author | Awadalla, P | |
dc.contributor.author | Grönroos, E | |
dc.contributor.author | Downward, J | |
dc.contributor.author | Jacks, T | |
dc.contributor.author | Carlsten, C | |
dc.contributor.author | Malanchi, I | |
dc.contributor.author | Hackshaw, A | |
dc.contributor.author | Litchfield, K | |
dc.contributor.author | TRACERx Consortium, | |
dc.contributor.author | DeGregori, J | |
dc.contributor.author | Jamal-Hanjani, M | |
dc.contributor.author | Swanton, C | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-06-23T13:11:48Z | |
dc.date.available | 2023-06-23T13:11:48Z | |
dc.date.issued | 2023-04-06 | |
dc.identifier | 10.1038/s41586-023-05874-3 | |
dc.identifier.citation | Nature, 2023, 616 (7955), pp. 159 - 167 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5854 | |
dc.identifier.eissn | 1476-4687 | |
dc.identifier.eissn | 1476-4687 | |
dc.identifier.doi | 10.1038/s41586-023-05874-3 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 159 - 167 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Adenocarcinoma of Lung | |
dc.subject | Air Pollutants | |
dc.subject | Air Pollution | |
dc.subject | Cell Transformation, Neoplastic | |
dc.subject | Environmental Exposure | |
dc.subject | ErbB Receptors | |
dc.subject | Lung Neoplasms | |
dc.subject | Particulate Matter | |
dc.subject | Particle Size | |
dc.subject | Cohort Studies | |
dc.subject | Macrophages, Alveolar | |
dc.subject | Alveolar Epithelial Cells | |
dc.title | Lung adenocarcinoma promotion by air pollutants. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-02-21 | |
dc.date.updated | 2023-06-23T13:11:18Z | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1038/s41586-023-05874-3 | |
rioxxterms.licenseref.startdate | 2023-04-06 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37020004 | |
pubs.issue | 7955 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Lung Cancer Group | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41586-023-05874-3 | |
pubs.volume | 616 | |
icr.researchteam | Cancer Genomics | |
icr.researchteam | Lung Cancer Group | |
dc.contributor.icrauthor | Houlston, Richard | |
dc.contributor.icrauthor | Turnbull, Clare | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Kevin Harrington) on 2023-06-23. Deposit type is initial. No. of files: 1. Files: Lung adenocarcinoma promotion by air pollutants.pdf | |