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Scientists reveal how air pollution can cause certain types of lung cancer

Like “a hidden killer”, air pollutants can trigger lung cancer in non-smokers via a mechanism uncovered in a study on Saturday, which experts say is an “important step for science and society”.

According to scientists from the Francis Crick Institute and University College London, fine particles – less than 2.5 microns, about the diameter of a hair – are already involved in climate change and are responsible for cancerous changes in cells in the respiratory tract.

Fine particles present in exhaust fumes, vehicle brake dust or fossil fuel fumes are “a hidden killer,” Charles Swanton of the Francis Crick Institute, which is in charge of the research, told AFP at the European Society’s annual congress for Medical Oncology, held in Paris.

While air pollution has long been suspected, ‘we weren’t sure if this pollution directly causes lung cancer or how,’ Professor Swanton said.

The researchers first looked at data from more than 460,000 residents in England, South Korea and Taiwan and showed that exposure to increasing concentrations of particulate matter was associated with an increased risk of lung cancer.
The most important discovery is that of the mechanism by which these pollutants can cause lung cancer in non-smokers.

Through laboratory studies in mice, the researchers showed that the particles caused changes in two genes (EGFR and KRAS) that have already been linked to lung cancer.

They then analyzed nearly 250 samples of healthy human lung tissue that had never been exposed to carcinogens from tobacco or heavy pollution. Mutations in the EGFR gene occurred in 18% of the samples, changes in KRAS in 33%.

“These mutations alone are probably not enough to lead to cancer. But if you expose a cell to pollution, it probably stimulates some kind of ‘inflammatory’ response, and if ‘the cell contains a mutation, it will form cancer'”. summarizes Professor Swanton.

It’s a “deciphering of the biological mechanism of what was a mystery,” but “quite puzzling,” acknowledges this Chief Medical Officer of Cancer Research UK, the study’s lead funder.

Traditionally, exposure to carcinogenic factors, such as those from cigarette smoke or environmental pollution, has been thought to cause genetic mutations in cells, rendering them tumorous and causing them to multiply.

For Suzette Delalog, director of the cancer prevention program at the Gustave Roussy Institute, “It’s quite revolutionary because we’ve had virtually no demonstration of this alternative carcinogenesis before.”

“This study is a pretty important step for science – and hopefully for society, too,” said the oncologist, who was responsible for discussing the study at the congress. “This opens a great door for knowledge, but also for prevention”.

The next step, according to Professor Swanton, will be ‘understanding why certain altered lung cells become cancerous after exposure to pollutants’.

This study confirms that reducing air pollution is also crucial for health, several researchers point out.

‘We have a choice about whether or not to smoke, but not the air we breathe. With probably five times more people exposed to unhealthy pollution than tobacco, this is a major global problem,’ said Professor Swanton.
According to the WHO, more than 90% of the world’s population is exposed to excessive particulate matter pollution.

This research also gives hope for new approaches to prevention and treatment.
For detection and prevention, Suzette Delalog considers several ways, but “not for tomorrow”: “personal assessment of our exposure to pollution”, detection – not yet possible – of the EGFR gene mutation, etc.

Tony Mok of the University of Hong Kong, quoted in an ESMO press release, said this research, “as fascinating as it is promising,” “allows us to consider using imaging to one day look for precancerous lesions in the lungs.” and then trying to treat them with drugs like interleukin-1 inhibitors.”

Professor Swanton envisions ‘what molecular cancer prevention might look like in the future, with one pill, perhaps every day, to reduce cancer risk in high-risk areas’.

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