Smoking, the leading cause of cancer in the world, is a considerable risk factor for the disease, mainly lung cancer. Tobacco smoke, in particular, would cause mutations in lung cells, which multiply abnormally during tumor formation. The risk would be multiplied by 10 or 15 for smokers (compared to non-smokers), but paradoxically, many “heavy smokers” never develop cancer. Only a minority of smokers get the disease: a real mystery to scientists. A new study published in the journal Nature Genetics suggests that this difference is related to complex genetic factors, with which some smokers are endowed, and that protect against cancer mutations.
Tobacco smoke can cause various harmful effects on lung cells. In the case of chronic obstructive pulmonary disease (COPD), for example, it irreversibly damages the progenitor cells of the lungs, preventing the renewal of functional cells that have been destroyed. However, in the case of tumor formation, these cells renew and multiply excessively.
There are several forms of lung cancer. The most common tumors (80 to 85% of cases) are known as “non-small cell” (referring to the size of the tumor cells). They can form in the cells of the glands in the outer parts of the lungs. In this specific case, it is an adenocarcinoma.
Also in the same category is squamous cell carcinoma, which usually develops in the cells of the bronchi and bronchioles, in the central parts of the lungs. There is also what is called large cell carcinoma, which can start anywhere in the lungs. Other rarer and no less serious forms of lung cancer include: (small cell lung cancer), soft tissue sarcoma, carcinoid, pleural mesothelioma.
Previous studies assumed that the excessive multiplication of lung cells during tumor formation was due to DNA mutations induced by tobacco smoke in healthy cells. The new study, conducted by researchers at the Albert Einstein College of Medicine in New York, USA, is the first to accurately quantify this mutation rate, thanks to a revolutionary and improved sequencing technique of the complete genomes of individual cells. .
Thanks to this new technique, researchers may finally have discovered why not all smokers develop cancer, and especially why many heavy smokers never develop the disease. The results could lead to new, more efficient and more specific diagnostic methods that help identify smokers who face a higher risk of contracting the disease and who require especially close surveillance.
” This may prove to be an important step towards prevention and early detection of lung cancer risk, and a far cry from the current herculean efforts needed to tackle late-stage disease, where most health care spending occurs. Said Simon Spivack, co-lead author of the study and professor of medicine, epidemiology, and population health and genetics at the Albert Einstein College of Medicine.
A more precise sequencing method
To quantify mutations in lung cells, the New York researchers developed a sequencing technique called single cell multiple displacement amplification (SCMDA). Typical single cell whole genome sequencing methods are quite limited in that errors can occur that make it difficult to identify true mutations. The new technique reduces the margins of error and better detects rare and random mutations.
Mutational landscapes of proximal bronchial basal cells from 33 individuals were then compared. 14 of them have never smoked and are between the ages of 11 and 86, while the other 19, between the ages of 44 and 81, have a maximum “smoking history” of 116 pack-years (PA) — 1 PA equals 1 pack of cigarettes smoked per day for a year. To give a specific example, a person who has smoked 40 cigarettes a day for 40 years will have a PA of 2 (2 packs) x 40 = 80 PA.
The cells of the participants were extracted by bronchoscopy. Proximal bronchial basal cells can survive for years or even decades and accumulate mutations with age that may be related to smoking. Also, of all the types of lung cells, they are among the most likely to become cancerous.
The researchers’ first discovery was the accumulation of mutations in the lung cells of non-smokers. These mutations would accumulate with age and would be more numerous in smokers. ” This experimentally confirms that smoking increases the risk of lung cancer by increasing the frequency of mutations, as previously assumed. Spivac says. Furthermore, the number of detected cell mutations increases linearly with the number of pack-years.
However, the increase in mutations appears to level off and stop after 23 pack-years. The heaviest smokers apparently and implausibly did not have the highest mutation rates. The researchers suggest that these people would have succeeded in suppressing the accumulation of mutations, because they would have very powerful systems to repair DNA damage and detoxify cigarette smoke. Soon, thanks to these discoveries, the group plans to develop new tests to measure a person’s ability to repair and detoxify their DNA.
Source: Nature Genetics
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