Particle-induced inflammation accelerates lung cancer progression

Particulate matter in polluted air can promote the development of lung cancer in people with a certain lung cancer mutation. This does not happen, as was always thought, because more DNA damage occurs, but through an entirely different process: an immune response to particulate matter in the lungs. This is evidenced by an extensive study among carriers of this mutation in four different countries.

The new insight that environmental factors can trigger cancer through inflammatory interactions provides starting points for approaches to combating this carcinogenesis. The study appeared Thursday in Science Magazine nature.

Most of them are smokers

The link between air pollution and lung cancer was already known: lung cancer is more common in areas with a lot of air pollution. But how air pollution can cause or promote cancer is still not fully understood.

Lung cancer is one of the most common types of cancer worldwide, and it is the third most common type of cancer in the Netherlands. Every year in the Netherlands, 14,000 people are diagnosed, and about 10,000 people die from it. There are many different shapes. The disease usually affects smokers, but people who have never smoked can also develop lung cancer. Often these are tumors with mutations in certain genes, such as in the EGFR (epidermal growth factor receptor) gene.

To better understand the role air pollution plays in lung cancer, cancer researchers led by British oncologist Charles Swanton focused on this type of cancer.

They analyzed data on nearly 33,000 people with lung cancer caused by an EGFR mutation from Canada, England, South Korea and Taiwan. The researchers considered exposure to particulate matter smaller than 2.5 micrometers (PM_2.5), which can penetrate the airways. They saw the same thing in every country: the higher the exposure to particulate matter in the living environment, the higher the incidence of this type of lung cancer. In the data from Canada, they can see exactly where people have lived during their lifetime. It showed that after three years of exposure to high concentrations of particles, 73 percent of virus carriers developed lung cancer, compared to 40 percent in the slightly exposed group.

No additional DNA damage

In laboratory mice that had been specially adapted to the mutation, the researchers studied how the particles might lead to tumor formation. To their surprise, the particles did not cause any further damage to the DNA in the lungs of the mice, as tobacco smoke does, for example. Instead, the molecules seemed to trigger an immune system response in the lungs that fuels tumor growth. It caused an influx of macrophages, immune cells that scavenge foreign material, into the lungs. In doing so, they release interleukin-1 beta. This substance stimulates cells lining the inside of the lungs that have mutated so that they form a tumor. Fewer tumors developed in mice that received antibodies to this substance while exposed to the particles.

These findings have major implications for the way we think about cancer prevention, writes geneticist Alan Balmain, who was not involved in the study, In an accompanying commentary. There is nothing doctors can do about mutations in cells, but blocking the process that determines the rate at which cancer develops can effectively prevent cancer. He points to several studies in mice that have shown that anti-inflammatories or healthy eating patterns that suppress chronic inflammation can prevent the growth of skin tumors. While society waits for measures to reduce air pollution, Balmain says the new insights could help shift the focus to diet and medication to prevent the development of cancers caused by inhaling polluted air.