Scientists have discovered how air pollution causes lung cancer in groundbreaking research that promises to rewrite our understanding of disease.
The findings describe how fine particles in car fumes “wake up” dormant mutations in lung cells and switch them into a cancerous state. This work helps explain why so many non-smokers develop lung cancer and is a ‘red flag’ about the harmful effects 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 has presented the findings at the European Society for Medical Oncology conference in Paris on Saturday.
“Globally, more people are exposed to dangerous levels of air pollution than the toxic chemicals found in cigarette smoke, and this new data links the importance of addressing the climate health and improving human health.”
Smoking remains the leading cause of lung cancer, but outdoor air pollution causes around one in 10 cases in the UK and around 6,000 people who have never smoked die from lung cancer every year. Globally, around 300,000 lung cancer deaths in 2019 were attributed to exposure to fine particles, called PM2.5, contained in air pollution.
However, the biological basis for how air pollution causes cancer is 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 – small errors that we accumulate in our DNA throughout life and that normally remain harmless.
“Obviously these patients have cancer without having mutations, so there must be something else,” said Swanton, who is also Cancer Research UK’s chief clinician. “Air pollution is associated with lung cancer, but people have largely ignored it because the underlying mechanisms were unclear.”
The latest work unveils this mechanism through a series of meticulous experiments showing that cells carrying dormant mutations can become cancerous when exposed to PM2.5 particles. The pollutant is the equivalent of the ignition spark from a gas hob.
In lab studies, Swanton’s team showed that mice that were engineered to carry mutations in a gene called EGFR, linked to lung cancer, were much more likely to develop cancer when exposed to the polluting particles. 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 the mice were given drugs to block the protein, they were less vulnerable to pollutants.
The work explains an earlier incidental discovery 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 preventative drugs, Swanton said.
The team also analyzed samples of healthy lung tissue, taken from patient biopsies, and found that the EGFR mutation was present in one in five normal lung samples. This suggests that we all carry dormant mutations in our cells that have the potential to turn into cancer – and chronic exposure to air pollution increases the chances of this happening.
“It’s a wake-up call about the impact of pollution on human health,” Swanton said. “You can’t ignore climate health. If you want to deal with human health, you must first deal with climate health.
Rosamund Kissi-Debrah, whose death of nine-year-old daughter Ella in 2013 was attributed by a coroner to illegal levels of air pollution, said there was still a “lack of common thought” about the pollution and health. “You can pump all the money you want into the NHS, but unless you clean the air more and more people will get sick,” she said. “My concern about global health is that every year we come up with 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 have long known about the link between pollution and lung cancer, and now we have a possible explanation. to that. As the consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate to tackle these issues, for both 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. “Air pollution and cigarette smoke contain many contributing substances. This has been known since the early 1960s but was basically ignored as everyone was focused on mutations,” he said. “Tobacco companies are now saying that smokers should switch to vaping because it reduces exposure to mutagens, and therefore the risk of cancer will disappear. That’s not true, because our cells mutate anyway, and there is evidence that vaping can induce lung disease and cause inflammation similar to promoters.