Lung adenocarcinoma promotion by air pollutants
| Title: | Lung adenocarcinoma promotion by air pollutants |
|---|---|
| Authors: | 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-Hanjani; Charles Swanton |
| Publication Year: | 2023 |
| Collection: | University of Leicester: Figshare |
| Subject Terms: | TRACERx Consortium; Macrophages; Alveolar; Animals; Mice; Lung Neoplasms; Cell Transformation; Neoplastic; Air Pollutants; Cohort Studies; Air Pollution; Environmental Exposure; Particle Size; Particulate Matter; ErbB Receptors; Alveolar Epithelial Cells; Adenocarcinoma of Lung |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| Language: | unknown |
| Relation: | 2381/24849837.v1; https://figshare.com/articles/journal_contribution/Lung_adenocarcinoma_promotion_by_air_pollutants/24849837 |
| Availability: | https://figshare.com/articles/journal_contribution/Lung_adenocarcinoma_promotion_by_air_pollutants/24849837 |
| Rights: | All Rights Reserved |
| Accession Number: | edsbas.99239B9F |
| Database: | BASE |