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Scientists discover how air pollution causes lung cancer

An international team of scientists has made a breakthrough in identifying how air pollution causes lung cancer in people who have never smoked, a development that could help medical experts prevent and treat tumors.

Researchers found that the fine particles in polluted air cause inflammation in the lungs, activating pre-existing cancer genes that were dormant. It was previously believed that air pollution caused genetic mutations that lead to cancer.

The findings are based on research led by the Francis Crick Institute in London and funded by Cancer Research UK Congress of the European Association of Medical Oncology Saturday in Paris.

As fewer people smoke, air pollution becomes more apparent as a cause of tumors in the lungs. An estimated 300,000 deaths from lung cancer worldwide are caused by very fine polluting particles with a diameter of less than 2.5 microns, known as PM2.5, which are emitted in vehicle exhaust and the combustion of fossil fuels.

“Our study fundamentally changed the view of lung cancer in people who have never smoked,” said project leader Charles Swanton. “Cells with cancer-causing mutations naturally accumulate as we age, but they are normally inactive. We have shown that air pollution wakes up these cells in the lungs, encouraging them to grow and potentially form tumors.”

The project is part of a £14mn Cancer Research UK program to understand how lung cancer starts and progresses. The scientists analyzed data on PM2.5 exposure and lung cancer in 400,000 people from the UK, Taiwan and South Korea and conducted lab experiments on mice, human cells and tissues.

Lung cancer cells under a microscope © Francis Crick Institute

Two major environmental carcinogens, tobacco smoke and ultraviolet light, damage DNA and create mutations that cause tumors. But the researchers found no evidence that PM2.5 particles directly mutate DNA, so they set out to find another explanation.

They found that the particles caused inflammation, which activated pre-existing mutations in genes that drive the development of many lung cancers.

“The mechanism we identified could ultimately help us find better ways to prevent and treat lung cancer in never-smokers,” Swanton said. “The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants, while others do not.”

The findings could apply to other cancers linked to air pollution, including mesothelioma and tumors of the throat and mouth, said Emilia Lim, another member of the Crick research team. “Ninety-nine percent of the world’s population lives in areas that exceed the World Health Organization’s annual limits for PM2.5, highlighting the public health problems of air pollution around the world,” she added.

One way to counteract the harmful effect of air pollution is to block a molecule called interleukin-1beta, which plays a key role in the inflammatory response to PM2.5. The team found that this approach worked in mice.

Tony Mok, a professor of medical oncology at the Chinese University of Hong Kong who was not involved in the study, said the study results were “intriguing and exciting”.

“It means we can ask if it will be possible in the future to use lung scans to look for precancerous lesions in the lungs and try to reverse them with drugs,” he said.

He joined Swanton and stressed the importance of reducing air pollution to reduce the risk of disease.

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