A long-term study funded by Cancer Research UK has revealed how air pollution can cause lung cancer in people who have never smoked.
Led by Professor Charles Swanton, our chief clinician, scientists at the Francis Crick Institute and University College London (UCL) have found that exposure to air pollution promotes the growth of cells carrying cancer-causing mutations in the lungs.
The research was presented by Professor Swanton today at the ESMO conference. It forms part of the TRACERx Lung Study, a £14 million programme funded by Cancer Research UK to understand how lung cancer starts and evolves over time, in the hope of finding new treatments for the disease.
Our study has fundamentally changed how we view lung cancer in never smokers.
– Professor Charles Swanton
The missing link
Although smoking remains the biggest risk factor for lung cancer, in the UK it is estimated that nearly 6,000 people who have never smoked die of lung cancer each year.i
Outdoor air pollution has been linked to variety of health problems, including asthma, chronic obstructive pulmonary disease (COPD), heart disease and dementia, and causes roughly 1 in 10 cases of lung cancer in the UK.
But unlike other environmental agents like UV light and tobacco smoke that directly mutate our DNA, how air pollution causes cancer to start in people who have never smoked has been a mystery up to now.
The researchers investigated the theory that tiny pollutant particles in the air smaller than 5% of the width of a human hair, called PM2.5, cause inflammation in the lungs that can lead to cancer.
Inflammation ‘wakes up’ normally inactive cells in the lungs that carry cancer-causing mutations. The combination of cancer-causing mutations and inflammation can trigger these cells to grow uncontrollably, forming tumours.
“Cells with cancer-causing mutations accumulate naturally as we age, but they are normally inactive,” says Swanton, who is also lead investigator on the TRACERx study.
“We’ve demonstrated that air pollution wakes these cells up in the lungs, encouraging them to grow and potentially form tumours.
“The mechanism we’ve identified could ultimately help us to find better ways to prevent and treat lung cancer in never smokers. If we can stop cells from growing in response to air pollution, we can reduce the risk of lung cancer.”
What did they do?
To make this discovery, the scientists examined a type of lung cancer called epidermal growth factor receptor (EGFR) mutant lung cancer. Mutations in the EGFR gene are commonly found in lung cancer in people who have never smoked.
They examined data taken from over 400,000 people from the UK and Asian countries, comparing rates of EGFR mutant lung cancer in areas with different levels of PM2.5 pollution.
They found higher rates of EGFR mutant lung cancer, as well as higher rates of other types of cancer, in people living in areas with higher levels of PM2.5 pollution.
“Even small changes in air pollution levels can affect human health,” says Dr Emilia Lim, co-author of the study and postdoctoral training fellow at the Francis Crick Institute and UCL.
“99% of the world’s population lives in areas which exceed annual WHO limits for PM2.5, underlining the public health challenges posed by air pollution across the globe.”
The team then exposed mice with cells carrying EGFR mutations in their lungs to air pollution at levels normally found in cities.
They found cancers were more likely to start from cells carrying EGFR mutations, compared with those mice not exposed to air pollution.
The researchers also showed that blocking a molecule called IL-1β, which normally causes inflammation and is released in response to PM2.5 exposure, prevents cancers from forming in these mice.
The research team think that the model presented in their study could be responsible for the early stages of many different types of cancer, where environmental triggers awaken cells carrying cancer-causing mutations in different parts of the body.
“Air pollution needs to wake up the right cells, at the right time, for lung cancer to start and grow,” says Dr William Hill, co-first author and postdoctoral training fellow at the Francis Crick Institute.
“Finding ways to block or reduce inflammation caused by air pollution would go a long way to reducing the risk of lung cancer in people who have never smoked, as well as urgently reducing people’s overall exposure to air pollution.”
Michelle Mitchell, our chief executive officer, added:
“Only by improving our fundamental understanding of the biology of lung cancer will we be able to offer better diagnosis and treatment, regardless of whether someone’s lung cancer is caused by smoking, air pollution or something else.
“It’s important to stress that smoking remains the biggest cause of lung cancer, responsible for around 7 in 10 lung cancers in the UK. Governments across the UK must do more to prevent lung cancers caused by smoking.
“They must introduce bold action to stop young people from starting to smoke, and provide funding for the measures and services needed to help people who smoke to quit.”
i. Bhopal A, Peake MD, Gilligan D, Cosford P. Lung cancer in never-smokers: a hidden disease. Journal of the Royal Society of Medicine. 2019;112(7):269-271. doi:10.1177/0141076819843654