Scientists discover how air pollution can trigger lung cancer in never-smokers – ScienceDaily

“The same particles in the air that originate from the burning of fossil fuels, which exacerbates climate change, directly affect human health via an important and previously overlooked carcinogenic 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 in. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and this new data links the importance of addressing climate health to improving human health,” said Charles Swanton, Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, who will present the research findings at the ESMO 2022 Presidential Symposium on Saturday 10 September.

The new findings are based on human and laboratory research on mutations in a gene called EGFR, which is seen in about half of people with lung cancer who have never smoked. In a 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 micrometers (μm) in diameter was associated with increased risk of NSCLC with EGFR mutations.

In the laboratory studies, Francis Crick Institute researchers showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells that had mutations in EGFR and in another gene linked to lung cancer called KRAS, driving them towards a cancer stem cell. like state. They also found that air pollution drives the influx of macrophages, which release the inflammatory mediator, interleukin-1β, which drives the expansion of cells with the EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited the initiation of lung cancer. These findings were consistent with data from a previous large clinical trial that showed a dose-dependent reduction in the incidence of lung cancer when humans were treated with the anti-IL1β antibody, canakinumab (4).

In a final series of experiments, the Francis Crick team used advanced, 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 cancer are actually present in normal lung tissue and are a likely consequence of aging. In our research, these mutations alone only weakly enhanced cancer in laboratory models . when lung cells with these mutations were exposed to air pollutants, we saw more cancers, and these arose faster than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer 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 do not,” Swanton said.

Commenting on the findings, Tony Mok of the Chinese University of Hong Kong, not involved in the study, said: “This research is exciting and exciting as it means we can ask whether in the future it will be possible to use lung scans to look for precancerous lesions in the lungs and try to reverse them with drugs such as interleukin-1β inhibitors. We do not yet know whether it will be possible to use high-sensitivity EGFR profiling on blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung scanning, so the discussions are still very speculative.”

Like Swanton, he emphasizes the importance of reducing air pollution to lower the risk of lung disease, including cancer. “We’ve known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As fossil fuel consumption goes hand in hand with pollution and CO2 emissions, we have a strong mandate to tackle these. problems — for both environmental and health reasons,” Mok concluded. A new mechanism has been identified through which very small pollutant particles in the air can trigger lung cancer in people who have never smoked, paving the way for new prevention methods and the development of treatments, according to the latest data [to be] reported at ESMO Congress 2022 by researchers from the Francis Crick Institute and University College London, funded by Cancer Research UK (1). The particles, typically found in vehicle exhaust and fossil fuel smoke, are associated with the risk of non-small cell lung cancer (NSCLC), which accounts for over 250,000 lung cancer deaths globally per year (2,3).

“The same particles in the air that originate from the burning of fossil fuels, which exacerbates climate change, directly affect human health via an important and previously overlooked carcinogenic 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 in. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and this new data links the importance of addressing climate health to improving human health,” said Charles Swanton, Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, who will present the research findings at the ESMO 2022 Presidential Symposium on Saturday 10 September.

The new findings are based on human and laboratory research on mutations in a gene called EGFR which is seen in about half of people with lung cancer who have never smoked. In a 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 micrometers (μm) in diameter was associated with increased risk of NSCLC with EGFR mutations.

In the laboratory studies, Francis Crick Institute researchers showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells that had mutations in EGFR and in another gene associated with lung cancer called KRAS, which drives them toward a cancer stem cell-like state. They also found that air pollution drives the influx of macrophages, which release the inflammatory mediator, interleukin-1β, which drives the expansion of cells with EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited lung cancer initiation. These findings were consistent with data from a previous large clinical trial that showed a dose-dependent reduction in the incidence of lung cancer when humans were treated with the anti-IL1β antibody, canakinumab (4).

In a final series of experiments, the Francis Crick team used advanced, ultra-deep mutational profiling of small samples of normal lung tissue and found EGFR and CRASH driver mutations in 18% and 33% of normal lung samples, respectively.

“We found that driving mutations in EGFR and CRASH genes commonly found in lung cancer are actually present in normal lung tissue and are a likely consequence of aging. In our research, these mutations alone only weakly enhanced cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers, and these arose faster than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer cells, which houses the driver. gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants, while others do not,” Swanton said.

Commenting on the findings, Tony Mok of the Chinese University of Hong Kong, not involved in the study, said: “This research is exciting and exciting as it means 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 drugs such as interleukin-1β inhibitors. We do not 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 the discussions are still very speculative.”

Like Swanton, he emphasizes the importance of reducing air pollution to lower the risk of lung disease, including cancer.

“We’ve known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As fossil fuel consumption goes hand in hand with pollution and CO2 emissions, we have a strong mandate to tackle these. question – for both environmental and health reasons,” concluded Mok.

References

1. LBA1 ‘Mechanism of Action and an Active Inflammatory Axis of Air Pollution Induced Non-Small Cell Lung Cancer in Never Smokers’ will be presented by Charles Swanton during President’s Symposium 1 on 10 September. Annals of OncologyVolume 33, Supplement 7, September 2022
2. Liu X, Mubarik S, Wang S. Lung cancer mortality attributable to long-term ambient particulate matter (PM_2.5) Exposure in East Asian countries during 1990-2019. Frontiers in Medicine 2021 Oct 15;8:742076
3. Turner MC, Andersen ZJ, Baccarelli A et al. Outdoor air pollution and cancer: an overview of the current evidence and public health recommendations. CA: Cancer J Clin 2020; 70: 460-479
4. Ridker PM, MacFadyen JG, Thuren T et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomized, double-blind, placebo-controlled trial. Lancet 2017 Oct 21; 390 (10105): 1833-1842