How does air pollution trigger non-small cell lung cancer? 

How does air pollution trigger non-small cell lung cancer? 
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A new mechanism shows very small pollutant particles in the air may cause non-small cell lung cancer in non-smokers. 

New research by scientists from Francis Crick Institute and University College London has revealed how air pollution could be causing non-small cell lung cancer and why this discovery is important for preventative care and the development of new treatments. 

The small particles, typically found in vehicle exhaust and smoke from fossil fuels, are associated with non-small cell lung cancer risk, which accounts for over 250,000 lung cancer deaths globally per year.   arch was presented at the European Society for Medical Oncology Congress 

Designing the study using 500,000 participants

The discovery was made using human and laboratory research on mutations in a gene called EGFR, which is found in around half of the people with non-small cell lung cancer who have never smoked. The study included almost 500,000 participants spanning across England, South Korea and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of non-small cell lung cancer EGFR mutations.   

“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. 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,” said Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK. 

The role of climate change in the prevalence of non-small cell lung cancer

In the laboratory studies, scientists from the Francis Crick institute showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells which had mutations in EGFR and in another gene linked to non-small cell lung cancer called KRAS, driving them towards a cancer stem cell-like state.  

Moreover, the researchers discovered that air pollution drives an increase of macrophages which subsequently release the inflammatory mediator, interleukin-1β, driving the expansion of cells with the EGFR mutations in response to PM2.5 exposure, and the blocking of interleukin-1β initiated non-small cell lung cancer. 

The findings were consistent with a previous large clinical trial which illuminated a dose dependant reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab. 

Finally, the team utilised ultra-deep 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 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. 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 is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” said Swanton.   

Commenting on the results, Tony Mok, the Chinese University of Hong Kong, not involved in the study, said: “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. 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.”  

Like Swanton, he stresses the importance of reducing air pollution to lower the risk of lung diseases, including cancer. “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,” Mok concluded.   



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