Journal Article

Lung adenocarcinoma promotion by air pollutants

Bakker, Bjorn, Chen, Yilun, Ghosh, Moumita, Veeriah, Selvaraju, Lee, Claudia, Martínez-Ruiz, Carlos, Troccoli, Clara I., Kuan, Feng-Che, Lavelle, Katrina, Bailey, Chris, Turnbull, Clare, Lee, Se-Hoon, Boumelha, Jesse, Li, Shijia, Suárez-Bonnet, Alejandro, McGranahan, Nicholas, Nagano, Ai, Jacks, Tyler, De, Swapnanil, Hackshaw, Allan, Magness, Alastair, Sivakumar, Monica, Naceur-Lombardelli, Cristina, Swanton, Charles, Huff, Ryan D., Awadalla, Philip, Caswell, Deborah R., Grönroos, Eva, Keith, Robert L., Lüchtenborg, Margreet, Rodrigues, Felipe S., Kanu, Nnennaya, Jamal-Hanjani, Mariam, Litchfield, Kevin, Chen, Kezhong, Myers, Renelle, Ryu, Min Hyung, Rowan, Andrew, Favé, Marie-Julie, Hill, William, Black, James R. M., Hill, Mark S., Houlston, Richard, Malanchi, Ilaria, Lim, Emilia L., George, Anthony M., Lam, Stephen, Karasaki, Takahiro, Pethick, Joanna, Carlsten, Christopher, Evans, Edward J., van Maldegem, Febe, Abbosh, Christopher, Lin, Meng-Hung, Downward, Julian, Cha, Hongui, Hardy, Steven, Merrick, Daniel T., McRonald, Fiona E., Marongiu, Fabio, Weeden, Clare E., Al Bakir, Maise, Miller, York E., Saal,

2023

Overview

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 μm (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-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  PM 2.5 air pollutants  and provide impetus for public health policy initiatives to address air pollution to reduce disease burden. Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/100 / 13/106 / 13/31 / 38 / 45 / 45/23 / 45/90 / 45/91 / 631/208/69 / 631/67/1612/1350 / 64 / 64/60 / 692/308/2778 / 692/499 / Adenocarcinoma / Adenocarcinoma of Lung - chemically induced / Adenocarcinoma of Lung - genetics / Air Pollutants - adverse effects / Air Pollutants - analysis / Air pollution / Air Pollution - adverse effects / Air Pollution - analysis / Alveolar Epithelial Cells - drug effects / Alveolar Epithelial Cells - pathology / Alveoli / Animal models / Animals / Cancer and Oncology / Cancer och onkologi / Carcinogens / Cell Transformation, Neoplastic - chemically induced / Cell Transformation, Neoplastic - drug effects / Cell Transformation, Neoplastic - genetics / Clinical Medicine / Cohort Studies / Environmental Exposure / Epidermal growth factor receptors / Epithelial cells / Epithelium / ErbB Receptors - genetics / Health care / Health policy / Health risks / Humanities and Social Sciences / Interleukins / Klinisk medicin / Lung cancer / Lung diseases / Lung Neoplasms - chemically induced / Lung Neoplasms - genetics / Macrophages / Macrophages, Alveolar - drug effects / Medical and Health Sciences / Medicin och hälsovetenskap / Mice / multidisciplinary / Mutation / Outdoor air quality / Particle Size / Particulate emissions / Particulate matter / Particulate Matter - adverse effects / Particulate Matter - analysis / Pollutants / Pollution control / Public health / Science / Science (multidisciplinary) / Smoking / Tumorigenesis / Tumors