Although tobacco is responsible for 80% of all lung cancer deaths worldwide, only a small number of people who smoke are actually affected by the disease. Scientists have been trying to figure out why, and now they have an answer in a study published in Nature Genetics. This suggests that certain people might have protection mechanisms against harmful mutations due to their addiction to tobacco.

This finding is significant because it may help to identify smokers more susceptible to lung cancer. Health networks could tighten medical control on these people. Simon Spivack (pulmonologist, professor at Albert Einstein College of Medicine, New York) said, "It might be an important step toward prevention and early detection of lung carcinoma risk."

The risk of contracting the disease is between 15 and 20 times higher for smokers than for the rest. It has been believed that smoking causes this type cancer through mutations in the DNA cells of the lungs. Jan Vijg, coauthor of the study and professor of Molecular Genetics, at the New York Center, says, "But it hadn't been possible to demonstrate until this study, because there was no way of accurately quantifying mutations in normal cells."

It is possible to make mistakes in the sequencing of a cell's DNA. These errors can be difficult to differentiate from mutations. Vijg overcame this hurdle by creating a sequencing method that minimizes errors and allows for the identification of mutations. It has been used by Vijg and his collaborators to study the effects of smoking on the lungs.

The cells in the lungs of 14 non-smokers aged 11 to 85 were compared with the cells of 19 smokers aged 44 to 81 who had smoked a maximum of 116 pack years. One pack-year equals one pack of cigarettes per year. These cells were taken from non-cancer diagnostic bronchoscopic examinations. These lung cells can survive for many years or even decades and can become mutated with time and smoking. They are the most susceptible to becoming cancerous of all cells in the lung," says Simon Spivack (pulmonologist, New York Center professor, and one of the study’s authors).

Researchers found that mutations accumulate in cells of non-smokers over time, but more in smokers. This experimentally confirmed that smoking increases lung cancer risk by increasing the frequency and severity of mutations. Spivack states that this is likely one reason why so few people who are not smokers develop lung cancer. However, 10% to 20% of those who smoke regularly get it.

With pack-years, the number of mutations increased and so did the risk of developing lung cancer. Surprisingly, however, the rate of mutations declined after 23 years of smoking. Older smokers had fewer mutations. "Our data suggests that these individuals have avoided further accumulation of mutations, which may explain why they survived so long despite heavy smoking. They may have excellent systems that repair DNA damage and detoxify cigarette smoke.

This discovery opened up new research avenues. Vijg says, "Now we want new assays to measure DNA repair and detoxification capacity of a person, which could offer new ways to assess lung cancer risk."