Smoking is a major risk factor for lung cancer. The harmful substances in cigarettes contribute to DNA mutations. However, heavy smokers do not necessarily carry more mutations than others, according to a study published in Nature Genetics. How can this be explained?
Although most lung cancers are caused by smoking, only a minority of smokers develop them. In the US, there are about 30.8 million adults, of whom around 10 to 20 percent will develop lung cancer in the future. In a study published in the journal Nature Genetics, researchers at Albert Einstein Medical School show that some smokers have a stronger mutation prevention system than others.
Screening for smoking-related DNA mutations
Lung cancer experts have long suspected that cigarette smoking contributes to cancer by causing mutations in the DNA of lung cells that, over time, accumulate into malignant cells. This claim was difficult to prove because of technical limitations. “However, it was not possible to prove this before this study because it was not possible to quantify the mutations in normal cells,” explains study co-author Jan Vijg, Ph.D.
The researchers did not have the ability to sequence the entire genome of a single cell without sequencing itself producing mutations that are then difficult to distinguish from true mutations caused by cigarette smoke. The technique, which has been refined by researchers at Albert Einstein Medical School, is called SCMDA. It was used on basal bronchial cells from 33 participants between the ages of 11 and 86, with different smoking histories. “These lung cells can live for many years, even decades, and therefore can accumulate mutations with age and smoking.
The formation and accumulation of mutations in DNA are normal processes, but exposure to cigarette smoke, which contains about 4,000 harmful substances, significantly increases the incidence of these phenomena. It seems clear that long-term smokers accumulate more mutations, which increases the risk of cancer. But that’s not what the researchers observed. “The heaviest smokers did not have the highest number of mutations. Our data suggest that these individuals survived as long as they did, despite heavy smoking, because they were able to avoid accumulating additional mutations.”
Correcting the mutations
This observation opens new avenues for investigating the efficiency of DNA repair mechanisms. It is currently difficult to assess the repair capacity of human DNA, but researchers hope to develop a test that makes this possible. This could be a way to assess lung cancer risk in addition to the parameters already known, such as duration of smoking, age when smoking started, and the number of packs per day.