The new findings are based on human and laboratory studies of mutations in a gene called EGFR that are found in about half of people with lung cancer who have never smoked. In a study of nearly half a million people living in the UK, South Korea and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometers (μm) in diameter had associated with an increased risk of NSCLC with EGFR mutations.
In laboratory studies, Francis Crick Institute scientists have shown that similar pollutant particles (PM2.5) promote rapid changes in airway cells with mutations in EGFR and in another lung cancer-associated gene called KRAS, prompting them to advance to a cancer stem cell. like status. They also found that air pollution promotes the outflow of macrophages that release an inflammatory mediator, interleukin-1β, which promotes the expansion of cells with EGFR mutations in response to exposure. with PM2.5 and interleukin-1β blockade inhibited lung cancer initiation. These findings are consistent with data from an earlier large clinical trial that showed a dose-dependent decrease in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab (4).
In a final series of experiments, the Francis Crick team used advanced, ultra-deep mutation profiles of small samples of normal lung tissue and found EGFR and KRAS driver mutations in 18% and 33% of lung samples were normal.
“We found that the driver mutations in the EGFR and KRAS genes, commonly found in lung cancer, are actually present in normal lung tissue and may be a consequence of the aging process. In our study, these mutations were only weakly carcinogenic in laboratory models.However, when lung cells with these mutations are exposed to air pollutants, we found more cancers and they occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes lung cancer initiation in cells “The next step is to discover why some mutated lung cells become cancerous when exposed to pollutants while others do not,” Swanton said.
Commenting on the results, Tony Mok, Chinese University of Hong Kong, who was not involved in the study, said: “This study is fascinating and exciting because it means we can question whether in In the future, it may be possible to use lung tomography to look for precancerous lesions in the lungs and try to reverse them with drugs like interleukin-1β inhibitors. whether highly sensitive EGFR profiles on blood or other samples can be used to find substances that not smokers are at increased risk of lung cancer and might benefit from lung scans, so discussions There’s still a lot of speculation.”
Like Swanton, he stressed 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 for it. Because fossil fuel consumption goes hand in hand with pollution and gases. carbon emissions, we have a strong mandate to address these issues, concludes Mok.