The mystery of heavy smokers who will never develop lung cancer has finally been solved?

grands fumeurs jamais cancer poumon

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Smoking, the leading cause of cancer in the world, is a significant risk factor for the disease, especially lung cancer. Tobacco smoke would mainly cause mutations in the lung cells – which multiply abnormally in the formation of tumors. The risk would multiply by 10 or 15 for smokers (compared to non-smokers), but paradoxically, many “heavy smokers” will never develop cancer. Only a minority of smokers become infected with this disease: it is a real mystery to scientists. New study published in the journal Genetics of nature suggests that this difference is related to the complex genetic factors that some smokers are endowed with and which protect against carcinogenic mutations.

Tobacco smoke can cause various harmful effects on lung cells. For example, in the case of chronic obstructive pulmonary disease (COPD), it irreversibly damages lung progenitor cells and prevents the recovery of destroyed functional cells. However, in the event of a tumor, these cells regenerate and multiply excessively.

There are several forms of lung cancer. The most common tumors (80 to 85% of cases) are tumors known as “non-small cell” (corresponding to the size of the tumor cells). They can form in glandular cells in the outer parts of the lungs. In this particular case, it is adenocarcinoma.

In the same category is also squamous cell carcinoma, which usually develops in bronchial and bronchiole cells, in the central parts of the lungs. There is also what is called large cell carcinoma that can start in any area of ​​the lung. Other, rarer and no less serious forms of lung cancer include: (small cell lung cancer), soft tissue sarcoma, carcinoid, pleural mesothelioma.

Previous studies have suggested that excessive lung cell proliferation during tumor formation was caused by DNA mutations in healthy cells caused by tobacco smoke. A new study by researchers at Albert Einstein College of Medicine (New York, USA) is the first to accurately quantify this rate of mutation, thanks to a revolutionary and improved sequencing technique for whole cell genomes.

Thanks to this new technique, scientists may have finally discovered why not all smokers develop cancer, and especially why many heavy smokers never develop the disease. The results could lead to new, more effective and targeted diagnostic methods to help identify smokers who are at increased risk of disease and who require particularly careful monitoring.

This may prove to be an important step towards the prevention and early detection of lung cancer risk and far removed from the current Herculean efforts needed to address the late stage of the disease, where most health care costs are incurred. “Said Simon Spivack, co-author of the study and professor of medicine, epidemiology and population health and genetics at the Albert Einstein College of Medicine.

More accurate sequencing method

To quantify mutations in lung cells, New York researchers have developed a sequencing technique called single-cell multi displacement amplification (SCMDA). Typical single-cell, whole-genome sequencing methods are severely limited in that errors can occur that make it difficult to identify true mutations. The new technique lowers error limits and better detects rare and random mutations.

Then, the mutational landscapes of the proximal bronchial basal cells of 33 individuals were compared. 14 of them have never smoked and are between the ages of 11 and 86, while another 19, aged 44 to 81, have a maximum “smoking history” of 116 packed years (PA) – 1 PA equals 1 pack of cigarettes smoked per day for one year. To give a specific example, a person who has smoked 40 cigarettes a day for 40 years will have an AP 2 (2 packs) x 40 = 80 AP.

Participants’ cells were removed by bronchoscopy. Proximal bronchial basal cells can survive for years or even decades and accumulate smoking-related mutations with age. In addition, of all lung cell types, they are among the most likely to become cancerous.


The scientists’ first discovery was the accumulation of mutations in the lungs of non-smokers. These mutations would accumulate with age and would be more frequent in smokers. ” This experimentally confirms that smoking increases the risk of lung cancer by increasing the frequency of mutations, as previously thought. says Spivack. In addition, the number of cell mutations detected increases linearly with the number of packet years.

However, the increase in mutations seems to be leveling off and stopping after 23 packet years. The heaviest smokers apparently and unlikely did not have the highest rate of mutations. The researchers suggest that these people would be able to suppress 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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