University of Leicester
428233_1_merged_1669149302.pdf (977.37 kB)

Lung adenocarcinoma promotion by air pollutants

Download (977.37 kB)
journal contribution
posted on 2024-02-22, 17:15 authored by W Hill, EL Lim, CE Weeden, C Lee, M Augustine, K Chen, FC Kuan, F Marongiu, EJ Evans, DA Moore, FS 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, DR Caswell, A Nagano, JRM Black, C Martínez-Ruiz, MH Ryu, RD Huff, S Li, MJ Favé, A Magness, A Suárez-Bonnet, SL Priestnall, M Lüchtenborg, K Lavelle, J Pethick, S Hardy, FE McRonald, MH Lin, CI Troccoli, M Ghosh, YE Miller, DT Merrick, RL Keith, M Al Bakir, C Bailey, MS Hill, LH Saal, Y Chen, AM George, C Abbosh, N Kanu, SH Lee, N McGranahan, CD 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, TRACERx consortium, JF Lester, A Bajaj, A Nakas, A Sodha-Ramdeen, K Ang, M Tufail, MF Chowdhry, M Scotland, R Boyles, S Rathinam, C Wilson, D Marrone, S Dulloo, DA Fennell, G Matharu, JA Shaw, J Riley, L Primrose, E Boleti, H Cheyne, M Khalil, S Richardson, T Cruickshank, G Price, KM Kerr, S Benafif, K Gilbert, B Naidu, AJ Patel, A Osman, C Lacson, G Langman, James DeGregori, Mariam Jamal-HanjaniMariam Jamal-Hanjani, Charles SwantonCharles Swanton
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.


Author affiliation

Department of Genetics and Genome Biology, University of Leicester


  • AM (Accepted Manuscript)

Published in







159 - 167


Springer Science and Business Media LLC





Copyright date


Available date


Spatial coverage