New evidence from a comprehensive study reveals that exposure to high concentrations of fine particles in the air can increase the risk of developing lung cancer in just 3 years.
The research also provides new insights into disease progression. It seems that the polluted haze is especially dangerous for healthy lung tissue, which is characterized by genetic changes that put it at risk of turning into cancer.
A study of nearly 33,000 people with lung cancer found that elevated levels of micropollutants were associated with an increased risk of EGFR-driven lung cancer, which primarily affects nonsmokers or people who don’t smoke heavily.
Charles Swanton, a cancer researcher from the Francis Crick Institute in the UK, says: “Cells with cancer-causing mutations naturally accumulate as we age, but they are usually inactive. We have shown that air pollution awakens these cells in the lungs, encouraging them to grow and possibly be tumors.”
The researchers say that these results confirm that air pollution is a major cause of lung cancer, and emphasize the need for action to reduce pollution and protect public health.
Particulate matter (PM) contributes to air pollution, affecting nearly every place on earth and causing 8 million deaths annually. Fine particles less than 2.5 micrometers (PM2.5) can reach deep into the lungs and have been linked to many health problems, such as heart disease and lung cancer.
“Traditionally, carcinogens are thought to cause tumors by causing direct DNA damage,” the study authors wrote in their published paper.
This new evidence supports the 76-year-old idea, as Swanton tweeted, “that cancer begins with two steps: acquisition of the driver (initiation) gene and then a second step where a cancer risk factor acts on these latent cells to cause disease.”
Mouse models also showed that exposure to air pollution caused changes in lung cells that might lead to cancer, with PM2.5 particles appearing to amplify the second step in the process.
To dig deeper into how air pollution causes cancer, Swanton and an international team of researchers conducted a 3-part analysis.
Using environmental and epidemiological data sets of 32,957 people from England, Taiwan and South Korea, they looked at levels of PM2.5 associated with EGFR-mutated lung cancer, which is caused by a mutation in the EGFR gene.
According to the results, the incidence of EGFR-mutated lung cancer increases with exposure to PM2.5. Additional data from 407,509 UK biobank participants supported this association.
A smaller data set of 228 non-smokers in Canada showed that following three years of exposure to high levels of PM2.5 air pollution, the risk of EGFR-induced lung cancer increased from 40% to 73%. This association was not found among the same Canadian group 20 years later.
Collectively, these data, together with published evidence, suggest that there is an association between EGFR-induced lung cancer incidence and levels of PM2.5 exposure and that 3 years of exposure to air pollution may be sufficient for this association to appear.
The team also used an induced mutation in EGFR in mouse models to look at the cellular processes that may be behind the growth of cancer in connection with air pollution. They found that PM2.5 appears to cause an influx of immune cells and the release of interleukin-1 (a signaling molecule that causes inflammation) into lung cells.
Moreover, blocking interleukin-1 during exposure to PM2.5 has been shown to stop the development of EGFR-induced cancers.
This evidence supports that PM2.5 may cause tumor growth and exacerbate cancer mutations that were already present. The researchers also found that lung cells called alveolar type II (AT2) cells are more likely to develop lung cancer when PM2.5 is present.
Finally, tests conducted on healthy lung tissue from 295 people revealed that a large percentage had genetic mutations that can lead to cancer, which means exposure to high levels of PM2.5 may put their health at greater risk.
“In summary, 54 out of 295 (18%) non-cancerous lung tissue samples harbored an EGFR driver mutation,” Swanton and co-authors wrote.
The researchers acknowledge that their work has some limitations. For example, mouse models of cancer prone to developing tumors even without PM2.5 may not show the full range of mutations found in healthy adult tissue. But they do give scientists a chance to study early tumor growth in a controlled environment.
Co-senior author and cancer cell biologist William Hill of the Francis Crick Institute concluded, “Finding ways to prevent or reduce inflammation caused by air pollution would go a long way in reducing the risk of lung cancer in people who have never smoked, as well as reducing people’s exposure to In general, air pollution is urgent.
