air pollution may explain why so many non-smokers get lung cancer

researchers find that small particles of air pollution can trigger lung cancer in cells with a specific mutation.

by dave yasvinski

published sep 13, 2022

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air pollution ‘promotes initiation of lung 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,” said tony mok, a professor at the chinese university of hong kong. getty

researchers have just uncovered the process by which small particles of air pollution are capable of triggering lung cancer, a discovery that may help explain why so many non-smokers still fall prey to the deadly disease. the research, which was presented at the european society for medical oncology’s esmo congress 2022, explains how these particles promote cancerous changes but also open up new avenues for novel forms of prevention and treatment.

“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 in london, who made the presentation. “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.”

the underlying mechanism at work relates to a gene called egfr that is present in half of all people with lung cancer who have never smoked. in a study of close to half a million people in england, south korea and taiwan, previous research found that exposure to increasing concentrations of particulate matter (pm) 2.5 micrometres (μm) in diameter was associated with an increased risk of non-small cell lung cancer in people with egfr mutations.

in the current study, researchers were able to show that these same particles are capable of promoting rapid changes in the cells lining the lungs of people with this mutation — and another gene linked to cancer called kras — by essentially pushing them toward a cancer stem cell-like state. they discovered that air pollution prompts an influx of macrophages that release inflammatory mediator interleukin-1β, driving the expansion of cells with egfr mutations in response to exposure to pm2.5. the team also performed a deep mutational profiling of samples of normal lung tissue and found egfr and kras mutations in 18 per cent and 33 per cent of these 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,” swanton said. “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.”

the findings open the door to new therapies that may be able to prevent cancer before it has a chance to take hold, according to tony mok, a professor at the chinese university of hong kong who was not involved in the study. “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.”

ultimately, the findings up the ante on taking a more serious approach to reducing air pollution before it has a chance to reduce the population any further. “we have known about the link between pollution and lung cancer for a long time and we now have a possible explanation for it,” mok said. “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.”