Study reveals how air pollution can trigger lung cancer in people who haven’t smoked

Recent research by a team of scientists at The Francis Crick Institute, presented at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris, shows an association between air pollution and lung cancer in non-smokers. The research was funded by Cancer Research UK and is part of the TRACERx Lung Study, which aims to understand lung cancer onset and progression.

background

While smoking remains the main risk factor for lung cancer, around 6,000 non-smokers in the UK succumb to lung cancer each year. Some of these cancer cases could be linked to air pollution.

A variety of respiratory diseases, such as asthma and chronic obstructive pulmonary disease, as well as heart disease and dementia, are linked to air pollution. In 2019, around 300,000 lung cancer deaths were attributed to particulate matter in the air. However, the role of air pollution in causing cancer is unclear, and there is no evidence that air pollution causes mutations in deoxyribonucleic acid (DNA).

About the study

In the present study, a team of scientists led by Professor Charles Swanton of the Francis Crick Institute examined epidemiological data from the UK and Asian countries to find correlations between levels of fine particulate matter in the air and the risk of lung cancer in people who had never smoked .

Given the absence of any DNA mutation signature in the lung cancer genomes of non-smokers, the researchers believe that the environmental airborne carcinogens cause lung cancer without causing DNA mutations. The team studied the role of air pollution in triggering lung cancer by exposing mouse models to different levels of pollution.

In addition, they used mouse models with mutations in the epidermal growth factor receptor (EGFR) and the viral oncogene homologue of Kirsten rat sarcoma (KRAS) in their lungs to understand the mechanisms, such as exposure to 2.5 diameter particulate matter µm (PM2.5) triggers lung cancer.

The researchers also used epidemiological data to compare EGFR mutation rates in areas with different levels of PM2.5 in the air. Mutations in the EGFR gene are prevalent in lung cancer in non-smokers.

Results

The study found a strong correlation in the epidemiological data between PM2.5 exposure and lung cancer among non-smokers in the UK, South Korea and Taiwan. Exposing mouse models with EGFR and KRAS mutations to different levels of air pollution also showed an increase in the number, size, and grade of cancers in the mice after exposure to air pollution.

In addition, the results showed that exposure to PM2.5 released interleukin 1β in the lung epithelial cells, causing pneumonia. Interleukin 1β converts epithelial cells with pre-existing EGRF or KRAS mutations into pseudostem cell-like progenitor cells and thus initiates tumor formation.

Biopsies of normal lung tissue also showed that EGFR and KRAS mutations are present in over 50% of normal lung samples. The authors believe that EGRF, KRAS and other cancer-causing mutations are ubiquitous in lung tissue and accumulate with age. In addition, comparisons using epidemiological data showed a greater incidence of EGFR-mutated lung cancer and other cancers in people living in areas with high levels of PM2.5 in the air.

Conclusions

In summary, the study links high levels of airborne PM2.5 to the incidence of lung cancer in people with no history of smoking. An accumulation of cancer-causing mutations in the cells is a normal aging process, according to the authors, and these mutations mostly remain inactive. Exposure to environmental agents such as PM2.5 stimulates interleukin 1β release, which leads to inflammation in the lung epithelium and triggers cells with cancer-causing mutations, such as EGFR and KRAS mutations, to initiate tumor formation.

The authors believe that the results of this study could help to understand the role of inflammation in the early stages of various other cancers, particularly in the absence of mutagenic signatures. The results of the study could also lead to better ways to reduce PM2.5-induced inflammation in the lung epithelium and treat lung cancer in people who have never smoked.

Although the risk of lung cancer associated with tobacco use is much higher than lung cancer associated with air pollution, nearly 95% of the world’s population is exposed to pollutants considered unsafe by the World Health Organization. Therefore, this improved awareness of the mechanisms behind air pollution-related lung cancer in non-smokers underscores the urgent need to reduce air pollution.