Scientists have discovered how air pollution causes lung cancer in groundbreaking research that promises to rewrite our understanding of the disease.
The findings describe how fine particles contained in car fumes “awaken” dormant mutations in lung cells and cause them to become cancerous. The work helps explain why so many non-smokers develop lung cancer and is a “wake-up call” to the harmful impact of pollution on human health.
“The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe,” said Professor Charles Swanton of the Francis Crick Institute, who presented the results at the European Society of 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 addressing climate health to improving human health.”
Smoking remains the leading cause of lung cancer, but outdoor air pollution causes about one in 10 cases in the UK, and an estimated 6,000 people who have never smoked die from lung cancer each year . Globally, approximately 300,000 lung cancer deaths in 2019 were attributed to exposure to fine particles, known as PM2.5, contained in air pollution.
However, the biological basis of how air pollution causes cancer is still unclear. Unlike smoking or sun exposure, which directly cause DNA mutations linked to lung and skin cancer, air pollution does not cause cancer by causing these genetic changes.
In contrast, people with non-smoking lung cancer tend to carry mutations that are also seen in healthy lung tissue: small mistakes that we accumulate in our DNA throughout life and that usually remain harmless.
“It’s clear that these patients have cancer without having mutations, so there must be something else going on,” said Swanton, who is also Cancer Research UK’s chief medical officer. “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 latent mutations can become cancerous when exposed to PM2.5 particles. The pollutant is the equivalent of the ignition spark from a gas stove.
In laboratory studies, Swanton’s team showed that mice that had been engineered to carry mutations in a gene called EGFR, linked to lung cancer, were much more likely to develop cancer when exposed to the particulate pollutants . They also revealed that the risk is mediated by an inflammatory protein, called interleukin-1 beta (IL1B), released as part of the body’s immune response to PM2.5 exposure. When mice were given drugs to block the protein, they were less vulnerable to pollutants.
The work explains an earlier incidental finding in a clinical trial of a heart disease drug by Novartis that people taking the drug, an IL1B inhibitor, had a marked reduction in the incidence of lung cancer . That could pave the way for a new wave of drugs to prevent cancer, 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 latent mutations in our cells that have the potential to turn into cancer, and chronic exposure to air pollution increases the odds of this happening.
“It’s a wake-up call about the impact of pollution on human health,” Swanton said. “Climate health cannot be ignored. If you want to address human health, you must first address climate health.”
Rosamund Kissi-Debrah, whose nine-year-old daughter Ella’s death in 2013 was blamed by a coroner on illegal levels of air pollution, said there continues to be a “lack of joint 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 are going to get sick,” he said. “My concern about global health is that every year we do the numbers: air pollution causes nine million premature deaths, but no one is held accountable.”
Professor Tony Mok, from the Chinese University of Hong Kong, who was not involved in the research, said: “We’ve known about the link between pollution and lung cancer for a long time and now we have a possible explanation for it. Because fossil fuel consumption goes hand in hand with pollution and carbon emissions, we have a strong mandate to address these issues, both for environmental and health reasons.”
Professor 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 promoter substances. This has been known since the early 1960s, but has essentially been ignored as everyone focused on mutations,” he said. “Tobacco companies are now saying that smokers should switch to vaping as this reduces exposure to mutagens and therefore the risk of cancer will disappear. This is not true as our cells get mutations anyway, and there is evidence that vaping can induce lung disease and cause inflammation similar to promoters.”
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