A comprehensive study of human health data and experiments on mice shows that air pollution may not be through DNA mutations, but by creating an inflammatory environment that “encourages” cells carrying cancer-causing mutations to proliferate, leading to cancer.
The study, published April 5 in Nature, sheds light on the mechanisms by which environmental exposures trigger cancer and hopes to find ways to prevent it.
“The idea is that exposure to carcinogens may cause cancer, but it doesn’t actually have any effect on DNA.” Serena Nik-Zainal, a medical geneticist at the University of Cambridge in the United Kingdom, said: “Not every carcinogen is a ‘mutagegen’. ”
Air pollution kills millions of people worldwide each year, including more than 250,000 from a type of lung cancer known as adenocarcinoma. Still, Nik-Zainal said, studying how air pollution causes cancer has been difficult, in part because the effects of air pollution are not as pronounced as other carcinogens, such as tobacco smoke or ultraviolet light.
To uncover this mechanism, Charles Swanton and colleagues at the Francis Crick Institute in the United Kingdom collected environmental and epidemiological data from the United Kingdom, Canada, South Korea, and Taiwan.
First, to reduce the impact of tobacco smoke on the data, the team focused on lung cancer that carries EGFR gene mutations. These mutations are more common in people who have never smoked than in smokers.
The results found that lung cancer carrying EGFR mutations was associated with exposure to air pollution in the form of PM2.5 or smaller inhalable particulate matter. This pollutant is emitted by internal combustion engines, coal-fired power stations and burning wood.
Then, to learn more, the researchers designed laboratory mice that carry EGFR mutations associated with human cancer. Mice exposed to particulate matter analogues found in air pollution were more likely to develop lung cancer than control mice not exposed to particulate matter.
However, despite the higher incidence of lung cancer, the number of mutations in mouse lung cells did not increase. Instead, after exposure to particulate matter, they showed signs of an inflammatory response that lasted for weeks. Some immune cells rushing to the lungs express a pro-inflammatory protein called IL-1β. Treating mice with an antibody that blocks IL-1β reduced the incidence of lung cancer.
Taken together, the findings suggest that air pollution promotes the proliferation of mutant cells already present in the lungs, which may be the result of the accumulation of DNA errors during aging.
“The main mechanism by which air pollution causes cancer is not the induction of new mutations, but the fact that this persistent inflammation becomes difficult to cure.” This is essential for these mutated cells to grow into tumors. University of California researcher Allan Balmain said.
Previous studies have found that cells carrying cancer-associated mutations are sometimes found in healthy tissue. Swanton and collaborators studied the frequency of EGFR mutations in noncancerous lung tissue and found that EGFR mutations are present in about one in every 600,000 cells.
“It’s rare, but it does exist.” One of the paper’s authors, Emilia Lim of the Francis Crick Institute, said.
This finding dovetails with previous findings by Balmain and collaborators. They tested 20 known or suspected human carcinogens and found that most of them did not increase the number of DNA mutations in mice. Balmain said: “There is a growing awareness that carcinogens do not have to function by directly altering the DNA sequence. ”
How can mutated cells be prevented from being activated by environmental factors such as air pollution? Balmain said that with millions of people exposed to high levels of air pollution, treatment with IL-1beta blocking drugs is not feasible and expensive, and can cause unwanted side effects in otherwise healthy people.
In his opinion, simple dietary interventions to fight inflammation may reduce the risk of certain cancers. “There is a need to revisit these issues and to study and test.” (Source: Wang Fang, China Science News)
Related paper information:https://doi.org/10.1038/s41586-023-05874-3
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