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Surprising research uncovers why most smokers don’t develop lung cancer

Шишкина Светлана/pexels

Lung cancer is mostly caused by cigarette smoking, however, not all smokers get the illness. Researchers from Albert Einstein College of Medicine suggest that certain smokers may have robust defensive mechanisms that restrict mutations and hence protect them from lung cancer in a new study published in Nature Genetics.

This finding may help identify smokers who need careful monitoring and are more likely to develop lung cancer.

Simon Spivack, M.D., M.P.H., a senior author of the study and a pulmonologist at Montefiore Health System, said, “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 suffering occur.”

Overcoming Challenges in Cell Mutation Research

Smoking is thought to cause lung cancer by causing DNA abnormalities in healthy lung cells over a very long period. This notion has not been proven until recently due to the absence of an exact way to measure mutations in normal cells. Due to the limitations of the available methods, this study was the first to provide evidence for the theory, according to Jan Vijg, Ph.D., a co-senior author of the study and professor and chair of genetics, ophthalmology, and visual sciences at Einstein.

A few years ago, Dr. Vijg, who is also associated with the Center for Single-Cell Omics at Jiaotong University School of Medicine in Shanghai, China, found a more effective method to circumvent this difficulty by sequencing the whole genomes of individual cells.

When employing single-cell whole-genome sequencing techniques to examine cells with uncommon and random mutations, sequencing mistakes may be a significant problem. It might be difficult to discern between these mistakes and actual alterations.

To solve this issue, Dr. Vijg created single-cell multiple displacement amplification (SCMDA), a novel sequencing method. This strategy lessens and accounts for sequencing mistakes, according to research in Nature Methods.

A total of 19 smokers, aged 44 to 81, with a maximum smoking history of 116 pack years, and 14 never-smokers, aged 11 to 86, were compared by the Einstein researchers to the mutational landscape of normal lung epithelial cells. The patients who donated the cells were having bronchoscopies for diagnostic purposes unrelated to malignancy.

One of the study’s researchers, Dr. Spivack, pointed out that these lung cells are among the most susceptible to cancer in the lung because they may get mutations over time as a result of age and smoking. The cells may last for many years if not decades.

Smoking Causes Mutations

Researchers have shown that as people age, both smokers and non-smokers get mutations (single-nucleotide variations and tiny insertions and deletions) in their lung cells. However, compared to non-smokers, smokers’ lung cells showed a much greater number of mutations. This finding lends credence to the idea that smoking raises the frequency of mutations, hence raising the risk of lung cancer. According to Dr. Spivack, this may be one of the reasons why lung cancer is less prevalent among nonsmokers while it affects 10% to 20% of lifetime smokers.

In addition, the number of lung cell mutations that were found rose in direct proportion to the number of pack years of smoking, suggesting an elevated risk of lung cancer. However, the surge of cell mutations peaked at 23 pack years of exposure, according to the researchers, suggesting that the number of mutations that may build up in lung cells is limited.

Dr. Spivack said that the people who smoked the most did not have the greatest burden of mutations. This suggests that these people may have been able to prevent the accumulation of further mutations, which allowed them to endure for a long time despite heavy smoking. According to Dr. Spivack, the mutation plateau may be due to their efficient mechanisms for repairing DNA damage or detoxifying cigarette smoke.

This discovery has led to a new line of inquiry. According to Dr. Vijg, they want to create innovative tests that can gauge a person’s potential for DNA detoxification or repair. This method could provide a fresh way to gauge the risk of lung cancer.

What effects does smoking have on your body?

Every organ in your body suffers damage from cigarette smoking, according to the Cleveland Clinic. In addition to nicotine, smoking tobacco exposes your lungs, blood, and organs to more than 5,000 chemicals, many of which are carcinogens (chemicals that cause cancer).

Smoking-related harm may dramatically reduce your longevity. In fact, smoking ranks first among factors that may be avoided in deaths in the US.

Smokers who are pregnant also put their unborn children in danger. Pregnancy-related side effects include:

Ectopic pregnancy, when the embryo implants outside the uterus, is a potentially fatal disorder.

Miscarriages.

Stillbirths.

birth flaws like cleft palates.

low weight at birth.

What additional problems might smoking exacerbate or cause?

The Cleveland Clinic claims that smoking causes several additional chronic (long-term) health issues that need continuing treatment in addition to its established dangers for cancer. The following specific smoking-related issues need treatment:

lower levels of HDL (the “good”) cholesterol and higher blood pressure, which both raise the risk of heart attack and stroke.

erection problems.

Lower oxygen delivery to the heart and other body tissues (rising risks for diabetes, peripheral artery disease, and coronary artery disease).

Colds come on more often, particularly in kids who live with smokers.

Having a harder time getting adequate oxygen results in COPD, asthma, bronchitis, or emphysema.

The research project’s full title is “Single-cell Analysis of somatic mutations in human bronchial epithelial cells in Relation to aging and Smoking.”

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