A new study looks at why many people smoking cigarettes do not develop lung cancer despite it being the main cause of the disease.
A study led by scientists at Albert Einstein College of Medicine suggests that some people smoking cigarettes may have robust mechanisms that protect them from lung cancer by limited mutations. The findings could help identify those smokers who face an increased risk for the disease and, therefore, need 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 Simon Spivack, MD, MPH, a co-senior author of the study, professor of medicine, of epidemiology & population health, and genetics at Einstein, and a pulmonologist at Montefiore Health System.
The findings were published online in Nature Genetics.
Studying cell mutations in people smoking cigarettes
It has been assumed that smoking cigarettes leads to lung cancer by triggering DNA mutations in normal lung cells. However, the researchers noted that this could not be proven until they carried out their study, which accurately quantified mutations in normal cells.
Jan Vijg, PhD, a study co-senior author and professor and chair of genetics, professor of ophthalmology and visual sciences, and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein overcame that obstacle when he developed an improved method for sequencing the entire genomes of individual cells.
Dr Vijg developed a new sequencing technique called single-cell multiple displacement amplification (SCMDA), which was reported in Nature Methods in 2017.
The research team used SCMDA to compare and collect the mutational landscape of normal lunch epithelial cells from two types of people: 14 people who had never smoked, aged 11 to 86, and 19 individuals who had been smoking cigarettes for a maximum of 116 pack-years. One pack-year of smoking equals one pack of cigarettes smoked per day for one year.
“These lung cells survive for years, even decades, and thus can accumulate mutations with both age and smoking,” said Dr Spivack. “Of all the lung cell types, these are among the most likely to become cancerous.”
Smoking and lung cancer
The researchers found mutations in the lung cells of non-smokers as they age, and significantly more mutations were discovered in the lungs of people smoking cigarettes.
“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesised,” said Dr Spivack. “This is likely one reason why so few non-smokers get lung cancer, while 10% to 20% of lifelong smokers do.”
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,” said Dr Spivack. “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 levelling off of mutations could stem from these people having very proficient systems for repairing DNA damage or detoxifying cigarette smoke.”
The finding has led to a new research direction. “We now wish to develop new assays that can measure someone’s capacity for DNA repair or detoxification, which could offer a new way to assess one’s risk for lung cancer,” said Dr Vijg.
