Editor’s Note: For more research on the links between air pollution and lung cancer, see Study Shows Shorter-Term Assessments Underestimate Pollution Exposure.

Investigators from the Francis Crick Institute and University College London may have identified a mechanism through which tiny pollutant particles may trigger lung cancer in people who have never smoked, according to late-breaking data¹ reported at the ESMO Congress 2022, which took place in September 9-13, 2022, in Paris.

The particles in question, which are typically found in vehicle exhaust and other sources of burning fossil fuels, are associated with non-small cell lung cancer (NSCLC) risk.

“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 Professor Charles Swanton, PhD, FRCP, who presented the late-breaking data.

“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.”

Dr. Swanton, who is principal group leader of the Swanton Lab at the Francis Crick Institute, said the findings are based on research of EGFR gene mutations, which are seen in about half of lung cancer patients who have never smoked. In the study of nearly half a million people living in 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 NSCLC with EGFR mutations.

The data showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells that had EGFR or KRAS gene mutations, driving them towards a cancer stem cell-like state. The research team also found that air pollution drives the influx of macrophages that release the inflammatory mediator, interleukin-1β, which drives the expansion of cells with the EGFR mutations in response to exposure to PM2.5.

These findings were consistent with data from a previous large clinical trial showing a dose-dependent reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab, Dr. Swanton said.

In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep 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,” said Dr. Swanton said. “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.”