[Reading Science] "'Nodam' Lung Cancer Without Genetic Cause?"

Air Pollutants Cause Lung Cancer Without DNA Mutation
Trigger Inflammation Leading to Proliferation of Existing Mutated Cells

"Why do people get lung cancer even if they don't smoke and have no family history?" Scientists have provided an answer to this question. They confirmed that air pollutants can cause lung cancer without causing genetic (DNA) mutations. Instead of the 'common sense' notion that cancer develops by mutating the DNA of normal cells into cancer cells, it triggers inflammation that promotes the proliferation of naturally occurring mutant cells, leading to cancer.

A research team at the Francis Crick Institute in London, UK, published these findings on the 5th in the international journal Nature. Cancer is generally known to develop when mutations occur in the genes of cells in the body due to genetic factors or carcinogens. This new study overturns that 'common sense.' It is believed that the findings can apply to other cancers caused by environmental factors like lung cancer and may help in developing preventive measures in the future. Serena Nik-Zainal, a medical geneticist at the University of Cambridge, told Nature, "Exposure to carcinogens can trigger cancer without affecting DNA," adding, "This suggests that not all carcinogens induce genetic mutations."

▲Lung cancer. [Photo by Asia Economy DB]

Air pollution kills millions worldwide every year, including over 250,000 lung cancer deaths. However, how air pollution triggers lung cancer differently from other causes like smoking or ultraviolet rays has not been well understood. The research team collected and analyzed environmental and epidemiological data from the UK, Canada, Korea, and Taiwan. To exclude lung cancer deaths caused by smoking, they focused on the presence of EGFR gene mutations, which are more commonly found in non-smokers than smokers among lung cancer patients. The results confirmed that lung cancer patients with EGFR gene mutations had been exposed to fine particulate air pollution. These are very small pollutants with diameters less than 2.5 micrometers (μm), about one-tenth the size of pollen grains. They are commonly emitted from internal combustion engines in cars, coal-fired power plants, and wood fires. To verify this, the team induced EGFR mutations in mice in the laboratory and exposed them to these particles, confirming that the mice had a higher probability of developing lung cancer compared to the control group.

What is more surprising is that despite the high lung cancer incidence, no increase in genetic mutations was observed in the lung cells of the mice. Instead, signs of persistent inflammatory responses appeared for several weeks after exposure to air pollution particles. Immune cells gathered in the mice’s lungs expressed an inflammation-promoting protein called IL-1β. When the researchers administered antibodies that block IL-1β protein, the incidence of lung cancer in the mice decreased.

These findings suggest that air pollutants promote the proliferation of existing mutant cells accumulated in the lungs during aging rather than inducing genetic mutations in normal cells. Alan Balmain, a professor at the University of California, USA, explained, "The main mechanism by which air pollution causes cancer is not the induction of new genetic mutations in cells," adding, "Chronic and persistent inflammation is essential for existing mutant cells to grow into tumors."

Previous studies have also revealed that cancer-causing mutant cells are often found in healthy tissues. In the case of EGFR mutations, they appear at a rate of about one in 600,000 normal lung cells. When inflammation caused by air pollution persists chronically, these cells can transform into tumors, proliferate, and cause lung cancer. Additionally, a 2020 study by the University of California team showed that administering 20 carcinogenic or suspected substances to mice mostly did not increase the number of DNA mutations.

The conclusion is that preventing the activation of existing mutant cells by environmental factors such as air pollution is key to lung cancer prevention. It is not feasible to administer drugs like IL-1β protein blockers to everyone exposed to harmful air pollutants, as they are expensive and may cause unwanted side effects. Scientists suggest that dietary interventions that reduce inflammation in the body could be a relatively practical and simple preventive measure. Professor Balmain said, "There is a need to study the best diet that can help prevent malignant diseases."