Small Pollutant Particles Associated With Lung Cancer Risk

According to research presented at the ESMO Congress 2022, a new mechanism has been recognized through which very small pollutant particles in the air may cause lung cancer in people who have never smoked.

The research was carried out by scientists from the Francis Crick Institute and University College London. It was funded by Cancer Research UK.

This opens the door to new prevention strategies and therapy development. The particles, commonly present in car exhaust and fossil fuel smoke, are linked to a higher risk of non-small cell lung cancer (NSCLC), which results in over 250,000 lung cancer deaths annually worldwide.

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.

Charles Swanton, Francis Crick Institute

Charles Swanton, also the Cancer Research UK Chief Clinician, adds, “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 link the importance of addressing climate health to improving human health.”

Charles Swanton presented the research results at the ESMO 2022 Presidential Symposium on September 10^th, 2022.

The new findings are supported by human and laboratory research on EGFR gene mutations, which are present in around 50% of lung cancer patients who have never smoked. In a study including over 500,000 persons who lived in England, South Korea, and Taiwan, exposure to rising levels of airborne particulate matter (PM) with a diameter of 2.5 μm was associated with a higher risk of developing NSCLC with EGFR mutations.

Researchers from the Francis Crick Institute demonstrated in laboratory investigations that the same pollutant particles (PM2.5) accelerated the transition of airway cells with EGFR and KRAS mutations into a state resembling cancer stem cells.

They discovered that exposure to PM2.5 causes an influx of macrophages to release the inflammatory mediator interleukin-1β, causing the proliferation of cells with EGFR mutations.

They also discovered that blocking interleukin-1β prevented the development of lung cancer. These results supported data from a clinical trial demonstrating a dose-dependent decrease in lung cancer incidence in patients receiving the anti-IL1 antibody canakinumab.

In a final set of tests, the Francis Crick team employed ultradeep mutational profiling to identify EGFR and KRAS driver mutations in 18% and 33% of normal lung tissue samples, respectively.

Swanton says, “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 aging. In our research, 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 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 harboring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t.

Charles Swanton, Francis Crick Institute

"This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1β inhibitors." Stated Tony Mok of the Chinese University of Hong Kong, who was not involved in the study.

We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative.

Tony Mok, Chinese University of Hong Kong

He emphasizes how crucial it is to reduce air pollution and the danger of lung conditions such as cancer.

Mok concludes, “We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues—for both environmental and health reasons.”