Scientists discover how air pollution acts as a trigger

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Air pollution has been linked to lung cancer in people who have never smoked before. Photographer DuKai/Getty Images
  • Researchers sought to understand the mechanism by which air pollution may induce non-small cell lung cancer in non-smokers.
  • They found that the fine particles trigger inflammation in the lungs and cause tumor formation by lung cells with pre-existing mutations.
  • This finding could pave the way for potential new approaches to lung cancer prevention and highlight the importance of reducing air pollution for human health.

The World Health Organization (WHO) reports that lung cancer was the most common cause of cancer death in 2020, accounting for 1.8 million deaths worldwide.

There are 2 main types of lung cancer, depending on the size of the cancer cells: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is much more common, representing 8 out of 10 lung cancer diagnoses.

It is a well established fact that smoking increases the risk of lung cancer. Yet about 10 to 20 percent of lung cancers occur in people who have never smoked or who have smoked fewer than 100 cigarettes in their lifetime, according to the Centers for Disaster Control and Prevention (CDC).

When a team of researchers from the Francis Crick Institute (FCI) and University College London (UCL) began studying “never smokers” who had developed non-small cell lung cancer, they noticed that most of them lived in areas where air pollution levels exceeded WHO guidelines.

Although air pollution has been associated with an incidence of lung cancer for at least two decades, the exact mechanism by which small polluting particles in the air cause lung cancer had not been identified.

Now the team of researchers from FCI and UCL, funded by Cancer Research UK, have identified a mechanism of non-small cell lung cancer driven by fine particulate matter (PM2.5) – particles of 2, 5 microns or less in diameter, which are commonly found in vehicle exhaust and fossil fuel smoke.

Researchers believe that PM2.5 triggers inflammation in the lungs and causes lung cells with pre-existing mutations to form a tumor.

“Cells with carcinogenic mutations naturally accumulate as we age, but they are normally inactive. We have demonstrated that air pollution awakens these cells in the lungs, encouraging them to grow and potentially form tumours.

– Dr Charles Swanton, Study Group Leader, Professor of Cancer Medicine at University College London, Senior Group Leader at the Francis Crick Institute and Chief Clinician at Cancer Research UK

Dr. Swanton presented these findings at ESMO 2022, the annual conference of the European Society for Medical Oncology, on September 10.

Dr. Howard L. (Jack) West, a specialist in thoracic oncology and associate clinical professor of medical oncology at the City of Hope Cancer Center, described the study as “a turning point in our understanding of environmental contributions to lung cancer in non-human patients.” -smokers”. .

Dr. Ross Camidge, director of thoracic oncology at the University of Colorado, said Medical News Today: “Air pollution was recognized as a cause of lung cancer in non-smokers by the WHO more than a decade ago […] will this idea change behavior more than the WHO announcement? No. But if [the] mechanism is robust, perhaps we will investigate prevention options in a new way.

The researchers started by looking at health data from 463,679 people in England, South Korea and Taiwan.

They found that exposure to PM2.5 pollution is correlated with the overall risk of lung cancer in non-smokers.

After identifying a correlation between air pollution and lung cancer, the researchers then set out to establish causation through laboratory studies in mice.

They found that exposure to air pollution caused a dramatic increase in the number, size and grade of cancers in mice with pre-existing mutations in the EGFR and KRAS genes.

This discovery confirms that pollution is not simply correlated with lung cancer, but may in fact be the cause.

The researchers found no evidence of DNA mutation due to environmental causes in the lung cancer genomes of non-smokers. Thus, they sought to understand how air pollution can cause cancer without causing DNA mutations.

They found that exposure to air pollution in mice and humans elicits an inflammatory response involving interleukin-1beta (IL1B) that transforms lung epithelial cells into a stem cell progenitor state. If the stem cell has the EGFR or KRAS mutation, there is an increased risk of tumor initiation.

In line with the conclusions of a previous major clinical testresearchers found that blocking IL1B with canakinumab (a monoclonal antibody) inhibited lung cancer initiation in mice.

Dr. Lecia Sequist, a Landry family professor of medicine at Harvard Medical School who specializes in lung cancer, who was not involved in the study, praised the researchers for this “monumental work” which brings together researchers and cancer patients to understand how lung cancer develops.

As the tumor is only initiated if the stem cell presents an EGFR or KRAS mutation, the researchers wanted to understand the origin of these mutations.

They performed lung biopsies in people who had never been exposed to carcinogens from smoking or heavy pollution. Even though the lungs were healthy, they found that 18-33% of the lung tissue samples contained carcinogenic mutations in the EGFR and KRAS genes.

Researchers believe that cancerous mutations increase with age in the lungs of non-smokers. They estimate that about 1 in 600,000 lung cells harbor a carcinogenic mutation.

“It takes pollution to turn the right cell, at the right time, in the right place, into cancer. I think this begins to explain the rarity of the disease but also the underlying risk of pollution […] in the world today,” said Dr Swanton in an interview at the ESMO Congress.

In April 2022, the WHO warned that almost all of the world’s population (99%) is exposed to dangerous levels of air pollution.

Dr Swanton said that, given the results of the study, reducing air pollution levels requires “an urgent mandate” and it has become very clear that “climate health and human health are intertwined”.

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