Particulate matter in air pollution may cause lung cancer in non-smokers

Exposure to particulate matter from air pollution appears to be associated with an increased risk Lung Cancer In those who have never smoked

Exposure to particulate matter from air pollution is a mechanism by which lung cancer can develop among individuals who have never smoked according to research findings presented in ESMO Conference 2022 By scholars from the Francis Crick Institute and University College London.

Globally in 2020, there were an estimated 2.21 million cases of lung cancer and 1.80 million deaths. There are two main types of lung cancer, small cell lung cancer and Non-small cell lung cancer (NSCLC) with this latter form accounts for about 84% of all cases. This has been recognized for several years Particulate matter in outdoor air pollution of at least 2.5 micrometers in size leads to an 18% increased risk of lung cancer among those who have never smoked. However, the mechanisms driving this increased risk among those who do not smoke have remained unclear.

In the study presented at the ESMO conference, researchers focused on lung cancers due to a mutation in the epidermal growth factor receptor (EGFR), a transmembrane protein tyrosine kinase receptor, expressed in certain normal epithelial tissue, mesenchyme, and nerve tissue. Furthermore, research indicates that EGFR protein expression is a risk factor in patients with NSCLC. Using normal lung tissue samples from humans and mice, the team investigated the consequences of increasing the concentration of 2.5 micrometers of particulate matter (PM2.5) with cancer risks.

Particulate matter exposure and cancer risk

Samples from 463,679 individuals were analyzed and the team found that increased PM2.5 levels were associated with greater risk for EGFR-modified NSCLC samples from England, South Korea and Taiwan. This was also associated with an increased risk of mesothelioma (hazard ratio, heart rate = 1.19), lung (heart rate = 1.16), anal (heart rate = 1.23), small intestine (heart rate = 1.30), and glioblastoma. Glial (HR = 1.19), lip, oral cavity and pharynx (HR = 1.15) and laryngeal carcinomas (HR = 1.26) in UK Biobank samples, per 1 μg/m3 PM2.5 increase.

An interesting finding was the presence of EGFR driver mutations in 18% of the normal lung samples and another mutation (KRAS) in 33% of the samples. The team also showed that PM enhanced the macrophage response and progenitor-like state in lung epithelium harboring the mutant EGFR. Consistent with NSCLC-promoting particles in compromised epithelium harboring driver mutations, PM increased tumor burden in three lung cancer models driven by EGFR or KRAS in a dose-dependent manner.

in Press release discussing their findingsCharles Swanton, who presented the findings at ESMO, said:We found that driving mutations in the EGFR and KRAS genes, commonly found in lung cancers, are already present in normal lung tissue and are a possible consequence of aging. In our research, these mutations alone weakly potentiate cancer in in vitro models. However, when lung cells infected with these mutations were exposed to air pollutants, we saw more cancers that occurred more quickly than when lung cells infected with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells that harbor driver. genetic mutations. The next step is to discover why some mutated lung cells turn cancerous when exposed to pollutants while others do not.

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Mechanism of action and hub of effective air pollution-induced inflammation in non-small cell lung cancer: Towards molecular cancer prevention