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Some smokers don’t get lung cancer;  Genetics might be why

May 12, 2022 — Some smokers may not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations or DNA changes that would make the cells malignant and turn them into tumors, the researchers said.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was difficult for them to identify mutations in healthy cells that could help predict future cancer risk, said Jan Vijg, PhD, lead study author and researcher at the University’s School of Medicine. of Shanghai, China, in a statement.

His team used a process called whole-genome single-cell sequencing to examine the cells lining the lungs of 19 smokers and 14 non-smokers aged from pre-teens to mid-80s. The cells came from patients who had tissue samples taken from their lungs during diagnostic tests unrelated to cancer. The scientists reported their findings in Natural genetics.

The researchers specifically looked at the cells that line the lungs, as these cells can survive for years and accumulate mutations over time related to aging and smoking.

“Of all types of lung cells, these are among the most likely to become cancerous,” says Simon Spivack, MD, lead study author and professor at Albert Einstein College of Medicine in New York.

Smokers had significantly more genetic mutations that can cause lung cancer than non-smokers, the analysis found.

“This experimentally confirms that smoking increases the risk of lung cancer by increasing the frequency of mutations, as previously assumed,” says Spivack. “That’s probably one of the reasons why so few non-smokers get lung cancer, while 10-20% of lifelong smokers have it.”

Among smokers, people had smoked for a maximum of 116 so-called pack-years. A pack-year is equivalent to smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, smokers’ lung cells did not appear to add more mutations, the researchers report, suggesting that some people’s genes may make them more likely to fight off mutations.

“The heaviest smokers did not have the highest mutation burden,” says Spivack. “Our data suggests that these people may have survived so long despite their heavy tobacco use because they were able to suppress the accumulation of mutations.”

While it’s possible that these discoveries could one day help doctors find better ways to detect lung cancer and treat the disease, that’s a long way off. Many more lab tests and larger studies will be needed to better determine which smokers might be more prone to lung cancer and why.

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