Why Do Some People Smoke All Their Life Without Getting Lung Cancer?

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Smoking is one of the most important risk factors for preventable diseases, disabilities and deaths worldwide. Smoking includes ordinary cigarettes, cigars, hookah, smokeless tobacco and electronic cigarettes, which can cause more than 8 million deaths every year. Smoking is also a major risk factor for cancer, especially lung cancer, which accounts for more than 14% of cancers worldwide. The risk of lung cancer in the lifetime of smokers is 22 times that of non-smokers. The more smoking, the higher the risk.

In 2020, a study published in JAMA oncology by the Centers for Disease Control and Prevention (CDC) and the American Cancer Society (ACS) showed that 50.8% of lung cancer patients were former smokers, 36.7% were current smokers, and only 12.5% were never smokers. In other words, 7 of every 8 patients with lung cancer are smokers.

However, in life, we will see that some "old smokers" who have smoked all their lives do not suffer from lung cancer. What's going on?

According to a study published in Nature Genetics, some smokers may have stronger DNA repair ability and better limit DNA mutations, so as to prevent lung cells from canceration and form malignant tumors.

Researchers from Albert Einstein College of medicine and other institutions in the United States analyzed the whole genome somatic mutation spectrum of proximal bronchial basal cells (pbbcs) of 33 participants in a single-cell dimension using single-cell multilocus amplification (scmda) sequencing technology.

Of the 33 participants, 14 were non-smokers aged 11-86, one of whom had lung cancer; The remaining 19 were smokers aged 44-81, including 7 former smokers and 12 current smokers, 14 of whom had lung cancer. Among the 19 smoking participants, the participants who smoked the most reached 116 packs / year (number of packs smoked per day [20 cigarettes per pack ] × Years of smoking).

Proximal bronchial basal cells are the most likely cells of all lung cell types to become cancerous. They can survive for years or even decades, and mutate with age and the accumulation of smoking.

After the whole genome library and sequencing of the proximal bronchial basal cells of the participants, the researchers analyzed the relevant data.

The results showed that the frequency of gene mutations increased with age, including single nucleotide variation (snvs) and small fragment insertion and deletion (indels). However, the frequency of mutations was significantly higher among smoking participants.

Among non-smoking participants, about 28 snvs events occurred per cell every year; Among the participants who smoked, about 91 snvs events occurred per cell every year, 63 more than those who never smoked.

For indels, the researchers also found an increasing trend with age among all participants. Among the participants aged 44-81 and smoking, the frequency of indels was higher than that of the same age and non-smoking participants.

Usually, more gene mutations mean a higher risk of cancer. This further confirms the view that smoking can lead to DNA mutations in lung cells, which can lead to lung cancer.

It should be noted that the researchers found that the frequency of gene mutations increased with the increase of smoking, but this linear correlation did not exist after 23 packs / year. The frequency of cell mutation in participants with heavy smoking (> 60 packs / year) was not significantly higher than that in participants with moderate smoking (20.1 packs / year - 60 packs / year).

According to the analysis of the researchers, this may be due to the enhanced adaptability of some people to mutation induction, more accurate or stronger DNA repair ability, and alleviating the toxicity of cigarette smoke.

In addition, the SBS (single base mutation) 4 mutation was present in smoking participants, but not in never smoking participants. Previous studies have confirmed that sbs4 mutation is the main feature of lung cancer patients who smoke. However, although the number of mutations in sbs4 increased significantly in smoking participants, this increase was not associated with age.

The researchers pointed out that the study confirmed the long-standing view that smoking does increase the frequency of gene mutations, thereby increasing the risk of lung cancer. This may be one of the reasons why few non-smokers will develop lung cancer, while 10% - 20% of lifelong smokers will develop lung cancer.

At the same time, the research also opens up a new research direction, hoping to develop a new detection method that can measure a person's DNA damage repair ability, which can provide a new method to assess a person's risk of lung cancer.

One of the study's corresponding authors, Simon D. of Albert Einstein School of medicine. Professor spivack said: "heavy smokers, although they smoke a lot, do not have more genetic mutations and can live longer, possibly because they have successfully inhibited the accumulation of further mutations. This may be due to their more accurate and powerful DNA damage repair system."

The study concluded by emphasizing that although some smokers may have a stronger ability to repair DNA damage, this does not mean that they will not suffer from lung cancer. Moreover, there is no way to detect who has a stronger ability to repair DNA damage.

Therefore, do not take risks. Non smoking is a healthier choice and one of the best ways to prevent lung cancer.

In a word, smoking will expose people to a large number of chemical carcinogens, such as polycyclic aromatic hydrocarbons, damage DNA, lead to gene mutation and cancer. Research shows that in addition to lung cancer, smoking also increases the risk of 17 different types of cancer, including urogenital cancer, head and neck cancer, digestive system cancer and hematological system cancer. At present, about 2.8 million cancers worldwide are related to smoking a year.

In addition, smoking is also associated with an increased risk of illness and death from a variety of diseases. For example, smokers have a doubled risk of stroke and a fourfold increased risk of heart disease; The life expectancy of lifelong smokers is reduced by at least 10 years.

For health and longevity, non-smokers should not try smoking; Smokers should quit smoking as soon as possible. The earlier they quit smoking, the more benefits they will get.

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