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Genetic mutations could be why some smokers never get lung cancer: Study

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Smoking cigarettes is widely known to be one of the biggest contributors to lung cancer, but some scientists have reported a new explanation as to why some smokers never develop the disease or even so much as a cough, in a new study published on Monday.

The study, led by scientists at the Albert Einstein College of Medicine in New York, found that some smokers may have robust mechanisms that protect them from developing lung cancer by limiting mutations.

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The researchers’ findings could help identify smokers that are at a higher risk of lung cancer and therefore warrant especially close monitoring.

It has long been assumed that cigarette smoking leads to lung cancer by triggering DNA mutations in normal lung cells. One of the doctors involved in the study, Dr. Jan Vijg, who is also a professor and chair of genetics, ophthalmology and visual sciences at the university, developed a new sequencing technique called single-cell multiple displacement amplifications SCMDA) to yield more accurate genomic sequencing results on the matter.

The researchers used SCMDA to “compare the mutational landscape of normal lung epithelial cells (cells lining the lung)” from two groups: 14 non-smokers who never smoked before between the ages of 11 and 86, and 119 smokers aged 44 to 81 who smoked a maximum of 116 pack years, according to the university’s statement.

The cells were then collected from patients who were undergoing bronchoscopy for diagnostic tests that were not related to cancer.

“These lung cells survive for years, even decades, and thus can accumulate mutations with both age and smoking,” said Simon Spivack, M.D., M.P.H., a co-senior author of the study, professor of medicine, of epidemiology & population health, and of genetics at Einstein, and a pulmonologist at Montefiore Health System. “Of all the lung’s cell types, these are among the most likely to become cancerous.”

The researchers found that mutations accumulated in the lung cells of non-smokers as they age and that many more mutations were found in the lungs of smokers.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” Spivack said. “This is likely one reason why so few non-smokers get lung cancer, while 10 percent to 20 percent of lifelong smokers do.”

He added that the heaviest smokers “did not have the highest mutation burden,” with data suggesting that these individuals “may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

“This leveling off of mutations could stem from these people having very proficient systems for repairing DNA damage or detoxifying cigarette smoke.”

The researchers also found that the amount of cell mutations seen in lung cells increased “in a straight line” with number of pack years spent smoking. This suggested that lung cancer risk increased at the same rate.

Despite those findings, the observed rise in cell mutations stopped after 23 pack years of smoke exposure.

“This may prove to be an important step toward the prevention and early detection of lung cancer risk and away from the current herculean efforts needed to battle late-stage disease, where the majority of health expenditures and misery occur,” Spivack said.

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