Scientists have discovered a new mechanism through which very small pollutant particles in the air may trigger lung cancer, even for those who have never smoked before.
This identification could now be used to develop new prevention measures or even therapies for lung cancer. The particles, which are typically located in the exhausts of vehicles and fossil fuel smoke, are associated with non-small cell lung cancer risk. This is the most common form of lung cancer, accounting for over 250,000 lung cancer deaths globally each year.
The identification of this mechanism and the possible development of therapies was reported at the European Society for Medical Oncology Congress (ESMO) 2022. The research was funded by Cancer Research UK and was carried out by scientists of the Francis Crick Institute and the University College London.
“The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells,” said Charles Swanton, the Francis Crick Institute and Cancer Research UK chief clinician.
“The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data sets link the importance of addressing climate health to improving human health.”
These new findings come from both human and laboratory research on mutations in a gene known as EGFR. These mutations are seen in about half of people with lung cancer who have never smoked.
Through a study of almost half a million people in England, South Korea and Taiwan, exposure to increasing concentrations of airborne particles was linked to increased risk of EGFR mutations, and non-small cell lung cancer risk.
These results were backed up by a laboratory study performed by Francis Crick Institute scientists. They showed that the same pollutant particles promoted rapid changes in airway cells which had EGFR mutations.
Another gene known as KRAS was also linked to lung cancer in these laboratory studies. They also found that air pollution increases the influx of macrophages (white blood cells that kill microorganisms and remove dead cells) which release the inflammatory mediator interleukin-1β.
This drives the expansion of cells with the EGFR mutations in response to exposure to particle matter. That blockade of interleukin-1β inhibited lung cancer initiation.
In a final collection of experiments, the Francis Crick team used ultradeep mutational profiling of small samples of normal lung tissue. They found EGFR and KRAS mutations in 18 per cent and 33 per cent of normal lung samples.
“We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models,” said Swanton.
“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 not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations.”
The next step for researchers will be to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t appear to.
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