Many people who have never smoked in their lives develop lung cancer. The reason is their exposure to high levels of pollution. However, until now the mechanisms through which very small pollutant particles present in the air can trigger lung cancer in these people were unknown. Now a study presented at the European Cancer Congress (ESMO 2022) conducted by scientists from the Francis Crick Institute and University College London (United Kingdom) has found how: pollution acts on inflammatory mechanisms that produce lesions that can become in cancer.
During the presentation of the results, Charles Swantondirector of the Francis Crick Institute and of the research warned: between 3 and 5 years of exposure is enough for this mechanism to be activated.
The information, which is also published in the “Annals of Oncology”, also paves the way for the design of new prevention approaches and the development of therapies.
The particles, which are normally found in vehicle exhaust fumes and smoke from fossil fuels, are associated with the risk of non-small cell lung cancer (NSCLC), accounting for more than 250,000 lung cancer deaths worldwide per year (2,3).
“The same airborne particles from fossil fuel combustion, which exacerbate climate change, are directly impacting human health through an important and previously overlooked cancer-causing mechanism in lung cells. The risk of lung cancer from air pollution is lower than from smoking, but we don’t have control over what we all breathe. Worldwide, more people are exposed to dangerous levels of air pollution than to toxic chemicals from cigarette smoke, and these new data link the importance of addressing climate health to improving human healthSwanton pointed out.
The new findings are based on research done both in people and in the laboratory on mutations in a gene called EGFR that are seen in about half of people with lung cancer who have never smoked.
In a study of nearly half a million people living in England, South Korea, and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometers (μm) in diameter was linked to an increased risk of lung cancer in non-smokers with EGFR mutations.
Air pollution drives the entry of macrophages that release the inflammatory mediator
In laboratory studies, scientists at the Francis Crick Institute showed that the same particulate matter (PM2.5) promoted rapid changes in airway cells that had mutations in EGFR and in another lung cancer-related gene called KRAS , causing them to become cancerous stem cells.
They further found that air pollution drives the influx of macrophages that release the inflammatory mediator, interleukin-1β, which drives the expansion of cells with EGFR mutations in response to PM2.5 exposure, and that blocking of interleukin-1β inhibits the initiation of lung cancer.
These findings were in line with data from a previous large clinical trial that showed a dose-dependent reduction in the incidence of lung cancer when people were treated with the anti-IL1β antibody, canakinumab.
The next step is to figure out why some lung cells with mutations become cancerous when exposed to pollutants, while others don’t.
Finally, this group used state-of-the-art ultra-deep mutational profiling of small normal lung tissue samples and found EGFR and KRAS driver mutations in 18% and 33% of normal lung samples, respectively.
«We found that driver mutations in the EGFR and KRAS genes, which are commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of aging. In our investigation, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and they occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in the cells that harbor the driver. genetic mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to contaminants, while others do not,” Swanton explained.
For Tony Mok of the Chinese University of Hong Kong (China), who was not involved in the study, it is a «intriguing and exciting research, as it means we may wonder if, in the future, it will be possible to use lung scans to look for precancerous lesions in the lungs and try to reverse them with drugs such as interleukin-1β inhibitors. We don’t yet know if it will be possible to use highly sensitive EGFR profiles in blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung screening, so discussions are still highly speculative.”
In any case, like Swanton, Mok stresses the importance of reducing air pollution to reduce the risk of lung diseases, including cancer. «We’ve known about the link between pollution and lung cancer for a long time, and now we have a possible explanation.. Since fossil fuel consumption goes hand in hand with pollution and carbon emissions, we have a strong mandate to address these issues, both for environmental and health reasons,” Mok concludes.