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Study Finds Air Pollution Can Cause Lung Cancer in People Who Never Smoked

Scientists in the UK have explained latest insights into how air pollution can cause lung cancer in people who have never smoked by 'waking up' cells that carry cancer-causing mutations.

The latest research suggested that environmental particulate matter measuring 2.5 μm or less (PM2.5) can promote lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue.

The research, first presented at the 2022 ESMO Congress in Paris, has since been peer reviewed and was published on Wednesday in the journal, Nature. Professor Charles Swanton from the Francis Crick Institute, who led the study, said the findings "fundamentally changed how we view lung cancer in people who have never smoked".

Although smoking remains the biggest risk factor for lung cancer, previous research has suggested that an estimated 10% to 25% of lung cancers worldwide occur in people who have never smoked. Air pollution has been linked to variety of health problems, including asthma, chronic obstructive pulmonary disease, heart disease, and dementia, but the mechanism for how it might cause cancer in people who have never smoked has not previously been explained.

Epidermal Growth Factor Receptor Cancer

Scientists at the Francis Crick Institute and University College London, who examined data from more than 400,000 people, found that higher rates of other types of cancer occurred in areas with high levels of PM2.5 pollution, which can be caused by engine exhaust fumes, cooking, industrial emissions, and burning household fuels.

In concentrating on epidermal growth factor receptor (EGFR) mutant lung cancer, which is more common in never-smokers or light smokers, the scientists found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in more than 400,000 people from England, South Korea, and Taiwan. Furthermore, cases of EGFR-driven lung cancer increased as levels of PM2.5 increased, they reported. 

Using mouse models, the researchers found that air pollutants caused an influx of macrophages into the lung and release of interleukin-1β, promoting cancer tumour growth.

Prof Swanton said the link between air pollution and lung cancer was not new, and the risk from smoking tobacco had been known about since the 1950s. He explained at a briefing hosted by the Science Media Centre (SMC) on Tuesday that "the relative risk of smoking and lung cancer is about 30-fold", and "the relative risk of air pollution and lung cancer somewhere between 1.2 and 2-fold". However, "many more people are exposed to environmental air pollution than they are to tobacco, and of course we have no choice over the air we breathe".

The findings of an association of air pollution with lung cancer were not new, Prof Swanton said: "What is new is the underlying mechanism that I think proves causation."

Towards Future Prevention

Dr William Hill, a postdoctoral researcher at the Francis Crick Institute, and the study's co-first author, said the results raised the prospect of finding preventative treatment. "Finding ways to block or reduce inflammation caused by air pollution would go a long way to reducing the risk of lung cancer in people who have never smoked, as well as urgently reducing people's overall exposure to air pollution," he said.

According to Prof Swanton: "If, let's say, you can take a tablet one day that could interfere with specific parts of the pathway without causing any toxicity – as we do, for instance, with statins and cardiovascular disease – I think there is hope for the future that this might be possible one day."

Commenting on the study to the SMC, Terry Tetley, professor of lung cell biology at the National Heart and Lung Institute, Imperial College London, said the scientists had produced "a fascinating study which brings together large-scale clinical data with basic science in animal models". Assessing the implications for the investigation, he said: "More work is needed to understand the mechanisms further, as well as identifying who may be at risk and ways to mitigate this."

Professor Dr Martin Göttlicher, director of the Institute of Molecular Toxicology and Pharmacology at the Helmholtz Centre in Munich, said it would be "interesting to see how the results presented here will find their way into the regulatory framework for air pollution control – both by supporting claims to reduce air pollution as well as with justified concepts for defining still tolerable particle amounts that are too low to trigger inflammatory reactions and thus should no longer have any relevant effect on human health."

Zongbo Shi, professor of atmospheric biogeochemistry at the University of Birmingham, said the study results "provides further evidence to reduce PM2.5 exposure to protect public health".

Michelle Mitchell, chief executive of CRUK, said: "These findings demonstrate that discovery science, which takes years of painstaking work, is changing our thinking around how cancer develops. Thanks to this research, we now have a much better understanding of the driving forces behind lung cancer in people who have never smoked."

Funding for the study was provided by Cancer Research UK (CRUK), the European Research Council, the Francis Crick Institute, the Mark Foundation, Lung Cancer Research Foundation, Rosetrees Trust, and the Ruth Strauss Foundation.