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Conducted by researchers at the Francis Crick Institute and University College London (both in London, UK), the study was funded by Cancer Research UK as part of the £14 million TRACERx Lung Study into how lung cancer begins and develops over time. Although smoking remains the biggest risk factor for lung cancer worldwide, an estimated 6000 people who have never smoked die from lung cancer every year in the UK, and around one in every ten cases of the disease is attributed not to smoking, but to air pollution.To better understand the connection, researchers studied data from 400 000 people from the UK and Asian countries to investigate the association between lung cancer with mutant EGFR—a mutation commonly found in people who have never smoked—and concentrations of particulate matter less than 2·5 μm in diameter (PM2·5) in the air. The results showed a positive correlation, with higher rates of EGFR-mutant lung cancer and other types of cancer found in areas with higher concentrations of PM2·5.
The researchers hypothesised that, when inhaled, PM2·5 particles, which measure about 3% of the width of a human hair, trigger an alarm response in the lungs, causing the inflammation and activation of dormant cells carrying cancer-causing mutations. To test their hypothesis, the team exposed mice with EGFR-mutant cells to air pollution concentrations normally found in cities, and found that the exposed animals were more likely to develop lung cancer than non-exposed mice.
“Our study has fundamentally changed how we view lung cancer in people who have never smoked”, observed lead investigator Charles Swanton (The Francis Crick Institute, London, UK). “Cells with cancer-causing mutations accumulate naturally as we age, but they are normally inactive. We’ve demonstrated that air pollution wakes these cells up in the lungs, encouraging them to grow and potentially form tumours.”
Lung cancer is also not the only cancer implicated in these findings. The research team believe that their model of environmental factors activating cells carrying cancer-causing mutations could be applicable to other types of cancer elsewhere in the body.
“According to our analysis, increasing air pollution levels increases the risk of lung cancer, mesothelioma, and cancers of the mouth and throat”, commented co-first author, Emilia Lim (The Francis Crick Institute). “This [finding] suggests a broader role for cancers caused by inflammation, triggered by a carcinogen like air pollution.”
The researchers also hypothesise, on the basis of the results from the preclinical part of the study, that blocking the lungs’ alarm response to PM2·5 might prevent this type of cancer from developing altogether.
“The mechanism we’ve identified could ultimately help us to find better ways to prevent and treat lung cancer in never-smokers”, explained Swanton. “If we can stop cells from growing in response to air pollution, we can reduce the risk of lung cancer.”
Co-first author, William Hill (The Francis Crick Institute), agreed. “Finding ways to block or reduce inflammation caused by air pollution would go a long way to reducing the risk of lung cancer in people who have never smoked, as well as urgently reducing people’s overall exposure to air pollution.”
However, the most urgent preventive measure demanded by these study findings is to reduce air pollution on a global scale in order to safeguard public health.
“In 2013, WHO’s International Agency for Research on Cancer classified outdoor air pollution generally, and airborne particles specifically, as human carcinogens”, commented expert Jonathan Samet (Colorado School of Public Health, Aurora, CO, USA). “The cancer burden from air pollution is substantial; Swanton and colleagues have added to the evidence supporting tighter air pollution control.”
Published: September 15, 2022
© 2022 Elsevier Ltd. All rights reserved.
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