Cigarette smoking causes lung cancer, yet only a minority of smokers develop the disease. Now, scientists at Albert Einstein College of Medicine, say that some smokers may have robust mechanisms that protect them from lung cancer by limiting mutations.
The findings say published in Nature Genetics could help identify those smokers who face an increased risk for the disease and therefore warrant especially close monitoring.
“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,” said Dr. Simon Spivack, 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.
The Einstein researchers compared the mutational landscape of normal lung epithelial cells (cells lining the lung) from two types of people: 14 never-smokers, ages 11 to 86; and 19 smokers, ages 44 to 81, who had smoked a maximum of 116 pack years. (One pack-year of smoking equals 1 pack of cigarettes smoked per day for one year.)
The cells were collected from patients who were undergoing bronchoscopy for diagnostic tests unrelated to cancer. “These lung cells survive for years, even decades, and thus can accumulate mutations with both age and smoking. Of all the lung cell types, these are among the most likely to become cancerous, “ said Spivack
The researchers found that mutations accumulated in the lung cells of non-smokers as they age — and that significantly more mutation were found in the lung cells of the smokers.
“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized. This is likely one reason why so few non-smokers get lung cancer, while 10 percent to 20 percent of lifelong smokers do,” said Spivack.
Another finding from the study: The number of cell mutations detected in lung cells increased in a straight line with the number of pack-years of smoking — and, presumably, the risk for lung cancer increased as well. But interestingly, the rise in cell mutations halted after 23 pack-years of exposure.
“The heaviest smokers did not have the highest mutation burden. Our data suggest 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,” said Spivack.