Cancer breakthrough is a ‘wake-up’ call about the danger of air pollution | cancer research

Scientists have discovered how air pollution causes lung cancer in groundbreaking research that promises to rewrite our understanding of the disease.

The findings outline how fine particles in car fumes “wake up” dormant mutations in lung cells, turning them into a cancerous state. The work helps explain why so many non-smokers get lung cancer and is a “wake-up call” about the harmful impact of pollution on human health.

“The risk of lung cancer from air pollution is lower than from smoking, but we can’t control what we all breathe,” said Prof. Charles Swanton of the Francis Crick Institute, who presented the findings at the European Society for Medical Oncology conference in Paris on Saturday.

“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 tackling climate health with improving human health.”

Smoking remains the leading cause of lung cancer, but outdoor air pollution causes about one in ten cases in the UK and an estimated 6,000 people who have never smoked die from lung cancer each year. Globally, in 2019, approximately 300,000 lung cancer deaths were attributed to exposure to particulate matter, known as PM2.5, in air pollution.

However, the biological basis for how air pollution causes cancer has remained unclear. Unlike smoking or sun exposure, which directly cause DNA mutations linked to lung and skin cancer, air pollution does not cause cancer by triggering such genetic changes.

Instead, people with non-smoking lung cancer tend to carry mutations that are also seen in healthy lung tissue — tiny mistakes that we accumulate in our DNA throughout life that normally remain harmless.

“Obviously these patients are getting cancer without having mutations, so there must be something else going on,” said Swanton, who is also chief physician at Cancer Research UK. “Air pollution is associated with lung cancer, but people have largely ignored it because the mechanisms behind it were unclear.”

The latest work reveals this mechanism through a series of painstaking experiments showing that cells carrying dormant mutations can become cancerous when exposed to PM2.5 particles. The contaminant is the equivalent of the ignition spark on a gas hob.

In lab studies, Swanton’s team showed that mice designed to carry mutations in a gene called EGFR, linked to lung cancer, were much more likely to develop cancer when exposed to the pollutant particles. They also revealed that the risk is mediated by an inflammatory protein called interleukin-1 beta (IL1B), which is released as part of the body’s immune response to PM2.5 exposure. When the mice were given drugs to block the protein, they were less vulnerable to the pollutants.

The work explains an earlier incidental finding in a clinical trial of a heart disease drug made by Novartis that people taking the drug — an IL1B inhibitor — had a marked reduction in the incidence of lung cancer. This could pave the way for a new wave of cancer-causing drugs, Swanton said.

The team also analyzed samples of healthy lung tissue taken during patient biopsies and found that the EGFR mutation was found in one in five of the normal lung samples. This suggests that we all carry dormant mutations in our cells that have the potential to become cancer – and chronic exposure to air pollution increases the chances of that happening.

“It’s a wake-up call about the impact of pollution on human health,” Swanton said. “You cannot ignore climate health. If you want to tackle human health, you have to tackle climate health first.”

A coroner named air pollution as one of the factors in the death of nine-year-old Ella Kissi-Debrah in 2013.
A coroner named air pollution as one of the factors in the death of nine-year-old Ella Kissi-Debrah in 2013. Photo: PA

Rosamund Kissi-Debrah, whose nine-year-old daughter Ella’s death in 2013 was attributed by a coroner to illegal levels of air pollution, said there is still a “lack of collective thinking” about pollution and health. “You can pump all the money you want into the NHS, but unless you clear the air, more and more people will get sick,” she said. “My concern about global health is that every year we make up the numbers – air pollution causes nine million premature deaths – but no one is held accountable.”

Prof Tony Mok, from the Chinese University of Hong Kong and who was not involved in the study, said: “We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. fossil fuels go hand in hand with pollution and carbon emissions, we have a strong mandate to address these issues, for both environmental and health reasons.”

Prof Allan Balmain, a cancer geneticist at the University of California, San Francisco, said the findings also had implications for our understanding of how smoking causes cancer. “Both air pollution and cigarette smoke contain many beneficial substances. This has been known since the early 1960s, but has essentially been ignored because everyone was focused on mutations,” he said. therefore the risk of cancer will disappear. This is not true, as our cells get mutations anyway, and there is some evidence that vaping can cause lung disease and cause inflammation similar to promoters.”

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