Lung cancer and air pollution

Study highlights danger urban populations face from air pollution. Photograph: Dan Kitwood/Getty

From The Guardian

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

The findings outline how fine particulates contained in car fumes “awaken” dormant mutations in lung cells and tip them into a cancerous state. The work helps explain why so many non-smokers develop lung cancer and is a “wake-up call” about the damaging 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 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 addressing climate health to improving human health.”

Smoking remains the biggest 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 of lung cancer every year. Globally, about 300,000 lung cancer deaths in 2019 were attributed to exposure to fine particulate matter, known as PM2.5, contained 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, those 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 which normally remain innocuous.

“Clearly these patients are getting cancer without having mutations, so there’s got to be something else going on,” 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 mechanisms behind it were unclear.”

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

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 far 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), 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 a previous incidental finding in a clinical trial of a heart disease drug, made by Novartis, that people on the drug – an IL1B-inhibitor – had a marked reduction in lung cancer incidence. This could pave the way for a new wave of cancer-preventing medicines, Swanton said.

The team also analysed 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 turn into cancer – and chronic exposure to air pollution increases the odds of that happening.

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

How about banning the sales of pure petrol/diesel cars?  Hybrids would cut emissions by 40-50%, plug-in hybrids by 80% and EVs by 100%.  Do we really care about the millions who die from burning fossil fuels, or not?