Lung adenocarcinoma promotion by air pollutants

William Hill, Emilia L. Lim, Clare E. Weeden, Claudia Lee, Marcellus Augustine, Kezhong Chen, Feng-Che Kuan, Fabio Marongiu, Edward J. Evans, David A. Moore, Felipe S. Rodrigues, Oriol Pich, Bjorn Bakker, Hongui Cha, Renelle Myers, Febe Maldegem, Jesse Boumelha, Selvaraju Veeriah, Andrew Rowan, Cristina Naceur-Lombardelli, Takahiro Karasaki, Monica Sivakumar, Swapnanil De, Deborah R. Caswell, Ai Nagano, James R. M. Black, Carlos Martínez-Ruiz, Min Hyung Ryu, Ryan D. Huff, Shijia Li, Marie-Julie Favé, Alastair Magness, Alejandro Suárez-Bonnet, Simon L. Priestnall, Margreet Lüchtenborg, Katrina Lavelle, Joanna Pethick, Steven Hardy, Fiona E. McRonald, Meng-Hung Lin, Clara I. Troccoli, Moumita Ghosh, York E. Miller, Daniel T. Merrick, Robert L. Keith, Maise Al Bakir, Chris Bailey, Mark S. Hill, Lao H. Saal, Yilun Chen, Anthony M. George, Christopher Abbosh, Nnennaya Kanu, Se-Hoon Lee, Nicholas McGranahan, Christine D. Berg, Peter Sasieni, Richard Houlston, Clare Turnbull, Stephen Lam, Philip Awadalla, Eva Grönroos, Julian Downward, Tyler Jacks, Christopher Carlsten, Ilaria Malanchi, Allan Hackshaw, Kevin Litchfield, James DeGregori, Mariam Jamal-Hanjani and Charles Swanton ()
Additional contact information
William Hill: The Francis Crick Institute
Emilia L. Lim: The Francis Crick Institute
Clare E. Weeden: The Francis Crick Institute
Claudia Lee: The Francis Crick Institute
Marcellus Augustine: The Francis Crick Institute
Kezhong Chen: University College London Cancer Institute
Feng-Che Kuan: Chang Gung Memorial Hospital, Chiayi Branch
Fabio Marongiu: University of Colorado Anschutz Medical Campus
Edward J. Evans: University of Colorado Anschutz Medical Campus
David A. Moore: The Francis Crick Institute
Felipe S. Rodrigues: The Francis Crick Institute
Oriol Pich: The Francis Crick Institute
Bjorn Bakker: The Francis Crick Institute
Hongui Cha: University College London Cancer Institute
Renelle Myers: University of British Columbia
Febe Maldegem: The Francis Crick Institute
Jesse Boumelha: The Francis Crick Institute
Selvaraju Veeriah: University College London Cancer Institute
Andrew Rowan: The Francis Crick Institute
Cristina Naceur-Lombardelli: University College London Cancer Institute
Takahiro Karasaki: The Francis Crick Institute
Monica Sivakumar: University College London Cancer Institute
Swapnanil De: University College London Cancer Institute
Deborah R. Caswell: The Francis Crick Institute
Ai Nagano: The Francis Crick Institute
James R. M. Black: University College London Cancer Institute
Carlos Martínez-Ruiz: University College London Cancer Institute
Min Hyung Ryu: Vancouver Coastal Health Research Institute, UBC
Ryan D. Huff: Vancouver Coastal Health Research Institute, UBC
Shijia Li: Vancouver Coastal Health Research Institute, UBC
Marie-Julie Favé: Ontario Institute for Cancer Research
Alastair Magness: The Francis Crick Institute
Alejandro Suárez-Bonnet: The Royal Veterinary College
Simon L. Priestnall: The Royal Veterinary College
Margreet Lüchtenborg: NHS England
Katrina Lavelle: NHS England
Joanna Pethick: NHS England
Steven Hardy: NHS England
Fiona E. McRonald: NHS England
Meng-Hung Lin: Chang-Gung Memorial Hospital
Clara I. Troccoli: University of Colorado Anschutz Medical Campus
Moumita Ghosh: University of Colorado Anschutz Medical Campus
York E. Miller: University of Colorado Anschutz Medical Campus
Daniel T. Merrick: University of Colorado Anschutz Medical Campus
Robert L. Keith: University of Colorado Anschutz Medical Campus
Maise Al Bakir: The Francis Crick Institute
Chris Bailey: The Francis Crick Institute
Mark S. Hill: The Francis Crick Institute
Lao H. Saal: SAGA Diagnostics
Yilun Chen: SAGA Diagnostics
Anthony M. George: SAGA Diagnostics
Christopher Abbosh: University College London Cancer Institute
Nnennaya Kanu: University College London Cancer Institute
Se-Hoon Lee: Sungkyunkwan University School of Medicine
Nicholas McGranahan: University College London Cancer Institute
Christine D. Berg: Early Cancer Detection Consultant
Peter Sasieni: Comprehensive Cancer Centre, King’s College London
Richard Houlston: Institute of Cancer Research
Clare Turnbull: Institute of Cancer Research
Stephen Lam: University of British Columbia
Philip Awadalla: Ontario Institute for Cancer Research
Eva Grönroos: The Francis Crick Institute
Julian Downward: The Francis Crick Institute
Tyler Jacks: David H. Koch Institute for Integrative Cancer Research
Christopher Carlsten: Vancouver Coastal Health Research Institute, UBC
Ilaria Malanchi: The Francis Crick Institute
Allan Hackshaw: Cancer Research UK and UCL Cancer Trials Centre
Kevin Litchfield: University College London Cancer Institute
James DeGregori: University of Colorado Anschutz Medical Campus
Mariam Jamal-Hanjani: University College London Cancer Institute
Charles Swanton: The Francis Crick Institute

Nature, 2023, vol. 616, issue 7955, 159-167

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41586-023-05874-3

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