By Mary Hearty
Although smoking tobacco is known to be the leading cause of lung cancer, accounting for 90% of the cases, there is a growing concern about non-smokers getting the disease due to air pollution.
A new study carried out by researchers at Cancer Research UK states that about 6000 cases of lung cancer in non-smokers in the UK are reported annually, equivalent to 10% of all the cases reported in the UK.
The study has revealed how air pollution can cause lung cancer in people who have never smoked.
Speaking during a media briefing hosted by UK Science Media Centre, Professor Charles Swanton, the lead researcher said environmental carcinogens are taken into the body through the air we breathe or food we eat, then they result in mutations in DNA and those mutations in DNA cause mutation in genes by chance and perhaps one of the mutations can affect the key gene that confers upon that cell growth advantage, which allows that cell to grow up into population cells in which second and third gene can lead to cancer formation.
Prof Swanton further noted that air pollutants do not just cause lung cancer. They affect multiple organs including the heart, brain, and pancreas among others, then result in stroke, type 2 diabetes, cardiovascular disease, and Alzheimer’s. Consequently, air pollution is responsible for about eight million deaths annually which are as many as tobacco.
“Air pollutants end up throughout the body, and macrophages take them up in the lining of multiple organs causing chronic inflammation. Through chronic inflammation, these macrophages and white cells metabolize them then release these inflammatory cytokines which possibly mediate tissue damage and certainly initiate lung cancer,” he explained.
The research which was done on 421 patients with lung cancer, where the researchers separated them into smokers and never-smokers, found that lung cancer in non-smokers has no carcinogen-induced DNA mutation signature and has a very low number of mutations.
Meaning they are unlikely to be environmental carcinogenic induced DNA mutation in this disease. So they concluded that if environmental air pollution is responsible for lung cancer, it would have to cause it in a way that is independent.
“We reasoned that it has to fulfill three criteria; first, it has to explain the geographic distribution of the disease, using EGFR mutant lung cancer which is the specific type of mutation human genome associated with lung cancer in never smokers as it is 4-5 times more common in lung cancer never smokers,” Prof. Swanton explained.
“The second criterion, then, was to prove that air pollution directly causes lung cancer; and how it could cause cancer without directly causing DNA mutations.”
Nevertheless, a study conducted in 2015 found that normal healthy tissue harbors mutant clones with cancer driver mutations with no evidence of cancer.
Also, according to a study done in 2020, 17 out of 20 environmental carcinogens tested in mice were found to drive cancer without causing DNA mutations.
So they reasoned that since lung cancer in never smokers is not associated with DNA mutations, could air pollution be inducing lung cancer; and could air pollution drive lung cancer specifically through inducing chemo promotion.
They also studied whether air pollution acts as a lung cancer promoter where they first looked into the geographical relationship between EGFRm lung cancer and PM2.5 pollution levels.
“We were able to get data from DEFRA for PM2.5 levels across the UK and we also worked with public health England to obtain EGFR lung cancer incidence levels. With these two, we were able to draw a correlation and found that they were positively associated. The same result was observed in a study done in Asia as well, although the air pollution levels were relatively higher compared to England,” he said.
To test how air pollution induces lung cancer, they found that mice exposed to the particulate matter had a significant increase in the number of preinvasive early lesions that were found in the mouse. Hence suggesting that the mouse model’s particulate matter cannot promote EGFR mutant homogenesis.
To test whether it was occurring through DNA mutations, they carried out sequencing of those tumors and found that there was no significant increase in the number of mutations that were present in air pollution-exposed tumors in the lesions. Hence suggesting that particulate matter is acting as an alternative mechanism.