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How can air pollution trigger lung cancer in non-smokers?

The new findings build on human and laboratory research on mutations in a gene called EGFR that is 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 associated with an increased risk of NSCLC with EGFR mutations.

In laboratory studies, scientists at the Francis Crick Institute showed that those same pollutant particles (PM2.5) promoted rapid changes in airway cells that had mutations in EGFR and in another gene linked to lung cancer called KRAS, making them Moved to cancer stem cells. like the state. They also found that air pollution increases the influx of macrophages that release the inflammatory mediator, interleukin-1β, leading to expansion of cells with EGFR mutations upon exposure to PM2.5, and that blockade of interleukin-1β is associated with lung cancer. stops the start. , These findings were consistent with data from a previous large clinical trial showing a dose-dependent reduction in the incidence of lung cancer when people were treated with the anti-IL1β antibody, canakinumab (4).

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In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep mutational profiling of small samples of normal lung tissue 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 commonly found in lung cancer are indeed present in normal lung tissue and are a possible consequence of aging. In our research, these mutations alone were only found in laboratory models. are weakly potent cancers. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were cells were not exposed to pollutants, suggesting that air pollution promotes the onset of lung cancer in cells harboring the driver gene mutation. The next step is to find out what causes exposure to pollutants. But why do some lung cells with the mutation become cancerous while others do not,” Swanton said.

Commenting on the results, Tony Mok, of the Chinese University of Hong Kong, not involved in the study, said: “This research is interesting and exciting because it means we can ask if, in the future, it is possible to use lung scans.” to look for pre-cancerous lesions in the lungs and try to reverse them with drugs such as interleukin-1β inhibitors. We do not yet know whether using highly sensitive EGFR profiling on blood or other samples Whether that would be possible. Smokers who are prone to lung cancer and may benefit from lung scanning, so the discussion is still very speculative.”

Like Swanton, he emphasized the importance of reducing air pollution to reduce the risk of lung diseases, including cancer. “We’ve long known about the link between pollution and lung cancer, and now we have a possible explanation for it. Since fossil fuel consumption goes hand in hand with pollution and carbon emissions, we have access to these. There is a strong mandate to tackle the issues – both for environmental and health reasons,” Mok concluded.

Source: Eurekalert

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