Why Some Heavy Smokers Manage To Avoid Lung Cancer Against The Odds

Scientists believe they may have found out why some smokers, against the odds, manage to avoid lung cancer.

Make no mistake: smoking tobacco is utterly terrible for you. Along with upping the risk of heart disease, diabetes, and strokes, the overwhelming majority of lung cancer cases are directly linked to smoking. Despite this risk, though, only 10 to 20 percent of lifelong smokers will actually develop lung cancer. Some people manage to smoke pack after pack of cigarettes for decades and somehow avoid lung cancer.

While this is influenced by sex, smoking status, and wider health, the ability of some smokers to dodge lung cancer might not just be a matter of sheer luck, according to the latest research.

In a study, reported in the journal Nature Genetics, scientists at Albert Einstein College of Medicine in New York argue that some smokers may have a robust mechanism or resilience that helps to limit mutations in the lungs that protect them from lung cancer.

It’s long been assumed that smoking leads to lung cancer by triggering DNA mutations in normal lung cells. As the team expected, the researchers found significantly more mutations in the lung cells of smokers as opposed to non-smokers.

It also appears that the number of cell mutations was closely linked to the amount the person had smoked – but only up to a point. Once the person had smoked 23 pack years (one pack year of smoking equals one pack of cigarettes smoked per day for one year) the rise in cell mutations stopped.

The study authors believe their bodies have some kind of system for repairing DNA damage or "detoxifying" smoke to make it less prone to causing mutations. However, more evidence is needed to confirm this explanation.

“The heaviest smokers did not have the highest mutation burden,” Dr Simon Spivack, co-senior author of the study and professor of medicine, of epidemiology, population health, and of genetics at Albert Einstein College of Medicine, said in a statement.

“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.”

The team reached their findings via a technique called single-cell multiple displacement amplification that can provide a more accurate depiction of peoples’ true mutations without introducing sequencing errors. They used this technique – which was only developed in 2017 – on the epithelial lung cells collected from 14 never-smokers, ages 11 to 86; and 19 smokers, ages 44 to 81, who smoked varying amounts.

If their findings hold true, this could offer a new strategy for the early detection of lung cancer risk. To follow up on this study, the team hopes to find out whether it’s possible to determine a person’s capacity for DNA repair or detoxification, thereby revealing the risk of them developing lung cancer from smoking.

“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,” explained Dr Spivack

“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.”

The article first appeared in April 2022.

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