•Researchers found that smokers had significantly more mutations in their lung cells than non-smokers.
•Researchers also found that human lung cell mutations accumulate with age.
Cigarette smoking is overwhelmingly linked to lung cancer, yet, only a small fraction of smokers develop the disease.
A study led by scientists at Albert Einstein College of Medicine and in Nature Genetics suggests that some smokers may have robust mechanisms that protect them from lung cancer by limiting mutations.
A mutation is a change in a DNA sequence. It can result from DNA copying mistakes made during cell division, exposure to ionizing radiation, exposure to chemicals called mutagens, or infection by viruses
The findings of the study could help identify smokers who face an increased risk for the disease and therefore warrant close monitoring.
"This may prove to be an important step towards 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.
Spivack is also a professor of medicine, epidemiology and population, health and genetics at Einstein. He is at the same time a pulmonologist at Montefiore Health System.
The researchers found that smokers had significantly more mutations in their lung cells than non-smokers.
Heavy smokers, however, did not have more mutations than less heavy smokers.
Spivack added that the heaviest smokers “did not have the highest mutation burden,” with data suggesting 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.”
Their study which was published in Nature, saw the researchers take lung and airway cell samples from 33 individuals:
- 12 adults without a smoking history ages 18–86 years
- 2 teenagers without a smoking history
- 19 smokers, including 7 former and 12 current smokers ages 44–81 years
The smokers reported smoking between 5.6 and 116 pack-years of cigarettes. One pack-year is equivalent to 20 cigarettes per day for one year.
The researchers noted that 14 of the 19 smokers were diagnosed with lung cancer alongside one non-smoker.
In the end, the researchers found that human lung cell mutations accumulate with age and that smokers have more mutations than non-smokers.
"This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized," said Dr Spivack.
"This is likely one reason why so few non-smokers get lung cancer, while 10% to 20% of lifelong smokers do."
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.
“So, if you’re smoking you should stop to decrease your risk. But for non-smokers, other than trying to live a healthy life, it’s, unfortunately, part of ageing. The study didn’t address this,” he explained.
When asked about limitations, Dr Onugha said: “The most glaring limitations are sample size and lack of age-matched cohorts.”