Lung adenocarcinoma promotion by air pollutants

Hill, W; Lim, EL; Weeden, CE; Lee, C; Augustine, M; Chen, K; Kuan, FC; Marongiu, F; Evans, EJ, Jr; 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; Martinez-Ruiz, C; Ryu, MH; Huff, RD; Li, S; Fave, MJ; Magness, A; Suarez-Bonnet, A; Priestnall, SL; Luchtenborg, M; Lavelle, K; Pethick, J; Hardy, S; McRonald, FE; Lin, MH; 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, SH; McGranahan, N; Berg, CD; Sasieni, P; Houlston, R; Turnbull, C; Lam, S; Awadalla, P; Gronroos, E; Downward, J; Jacks, T; Carlsten, C; Malanchi, I; Hackshaw, A; Litchfield, K; TRACERx Consortium; DeGregori, J; Jamal-Hanjani, M; Swanton, C

Author(s): Hill, W; Lim, EL; Weeden, CE; Lee, C; Augustine, M; Chen, K; Kuan, FC; Marongiu, F; Evans, EJ, Jr; 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; Martinez-Ruiz, C; Ryu, MH; Huff, RD; Li, S; Fave, MJ; Magness, A; Suarez-Bonnet, A; Priestnall, SL; Luchtenborg, M; Lavelle, K; Pethick, J; Hardy, S; McRonald, FE; Lin, MH; 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, SH; McGranahan, N; Berg, CD; Sasieni, P; Houlston, R; Turnbull, C; Lam, S; Awadalla, P; Gronroos, E; Downward, J; Jacks, T; Carlsten, C; Malanchi, I; Hackshaw, A; Litchfield, K; TRACERx Consortium; DeGregori, J; Jamal-Hanjani, M; Swanton, C;
Details: Publication Year 2023,Volume 616,Issue #7955,Page 159-167
Journal Title: Nature
Publication Type: Research article
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(1). Here we propose that environmental particulate matter measuring </=2.5 mum (PM(2.5)), 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-1beta. 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: Animals; Mice; *Adenocarcinoma of Lung/chemically induced/genetics; *Air Pollutants/adverse effects/analysis; *Air Pollution/adverse effects/analysis; *Cell Transformation, Neoplastic/chemically induced/drug effects/genetics; Environmental Exposure; ErbB Receptors/genetics; *Lung Neoplasms/chemically induced/genetics; Particulate Matter/adverse effects/analysis; Particle Size; Cohort Studies; Macrophages, Alveolar/drug effects; Alveolar Epithelial Cells/drug effects/pathology
Department(s): Laboratory Research
PubMed ID: 37020004
Publisher's Version: https://doi.org/10.1038/s41586-023-05874-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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