Cigarette smoking is a major cause of excessive lung cancer, yet only a small number of smokers develop the disease. A study led by scientists at the Albert Einstein College of Medicine and published online today Nature genetics Suggests that some smokers may have strong mechanisms that limit mutations and protect them from lung cancer.
The results could help identify smokers who are at increased risk for the disease and therefore require particularly intensive monitoring.
Overcoming barriers to the study of cell mutations
It has long been thought that smoking triggers DNA mutations in normal lung cells and leads to lung cancer.
“But this could never be proven until our study, since there was no way to accurately measure mutations in normal cells,” said Jan Viz, PhD, a research co-author.
Single-cell whole-genome sequencing methods can introduce sequencing errors that are difficult to distinguish from true mutations – a serious error when analyzing cells containing rare and random mutations. Dr. Vizg solves this problem by developing a new sequencing technique called Single-Cell Multiple Displacement Amplification (SCMDA).
As reported The method of nature In 2017, this method is responsible for and reduces the sequencing error.
Using SCMDA, Einstein researchers compared the mutational landscape of normal lung epithelial cells (i.e., lining cells of the lungs) between two types of people: 14 people who never smoke, ages 11 to 86; And 19 smokers, ages 44 to 81, who smoked a maximum of 116 pack years. (One pack of cigarettes is equivalent to 1 pack of cigarettes smoked per day for one year a year.) The cells were collected from patients who underwent bronchoscopy for diagnostic tests that were not related to cancer.
“These lung cells survive for years, even decades, and thus accumulate mutations with both age and smoking,” Dr. Spivak added. “Of all the types of lung cells, these are the most likely to get cancer.”
Mutations caused by smoking
Researchers have found that mutations (single-nucleotide variations and small insertions and deletions) accumulate in the lung cells of smokers as they age – and significantly more mutations are found in the lung cells of smokers.
“This empirically confirms that smoking increases the risk of lung cancer by increasing the frequency of mutations, as previously estimated,” said Dr. Spivak. “This is probably one of the reasons why very few smokers get lung cancer, where 10% to 20% of lifelong smokers do.”
Another finding from the study: The number of cell changes detected in lung cells has increased in a straight line with the number of smoking pack years – and, presumably, the risk of lung cancer has also increased. But the funny thing is, after 23 pack years of exposure, the growth of cell mutations stops.
“The heaviest smokers didn’t understand the most mutations,” Dr. Spivak added. “Our data suggest that these individuals may have survived so long despite their heavy smoking because they were able to suppress further mutation deposits. This level of mutation may be due to the fact that these people have highly efficient systems for repairing DNA damage or detoxifying cigarette smoke. ”
The search led to a new study. “We now want to create new aces that can measure someone’s ability to repair or detoxify DNA, which could offer a new way to assess one’s risk for lung cancer,” Dr. Viz added.
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