The reason why the "old smoking gun" does not suffer from lung cancer has been found! Do you have this "detoxification gene"?

"A pack of cigarettes a day, happy like a god" is a realistic portrayal of many old smokers. Smoking may be to alleviate anxiety and tension, or to socialize to gain group acceptance, or to seek stimulation to refresh the mind, but at the same time smoking will cause physical dependence and affect physical health. Intuitively, long-term smoking can induce DNA mutations in lung cells, which in turn can lead to lung cancer. Although 70% of smoking-related lung cancer deaths occur in the elderly, there are still a large proportion of "old smoking guns" that do not have lung cancer, so what are the "superpowers" of these "surviving" "old smoking guns"? A new study in the Journal of Nature will reveal the answer.

Long-term smoking without lung cancer

Stemming from the ability to limit genetic mutations

On April 11, 2022, the research team of the Albert Einstein School of Medicine in the United States published a study entitled "Single-cellanalysis of somatic mutations in human bronchial epithelial cells in relationto aging and smoking" at Nature Genetics. Studies have found that some long-term smokers may have some powerful ability to limit DNA mutations and protect them from lung cancer.

Figure 1 Research results (Source: [1])

The risk of lung cancer in smokers depends on the dose smoked, but it is unclear whether this increased risk depends on an increase in the rate of accumulation of somatic mutations in normal lung cells. In this study, the researchers used single Cell Multiplex Displacement Amplification (SCMDA) technique to measure bronchoscopic lung cells collected from 14 never-smokers aged 11 to 86 and 19 smokers aged 44 to 81 years (smoking average of 116 packs per year) and generated Proximal Bronchial Single-cell genome-wide somatic cell mutation profiles from Basal Cells, PBBCs), quantitative analysis of mutational loads of individual bronchial epithelial cells caused by progressive age and lifetime exposure to tobacco smoke to dissect the respective effects of these two key carcinogenic factors.

The results were found

1. The cumulative mutation of PBBCs in non-smokers increases with age;

2. The cumulative mutation of PBBCs in smokers also increases with age, but the mutation rate increases significantly;

3. The number of PBBCs cell mutations increases linearly with the increase of smoking dose, so that the risk of lung cancer is also significantly increased. Surprisingly, no further increase in the rate of mutation was observed after the smoking volume reached 23 packs;

4. People who smoke the most do not necessarily have the highest mutation load, and intrinsic factors such as reducing DNA damage by improving the accuracy of DNA repair or through detoxification of tobacco smoke, thereby inhibiting mutation accumulation and reducing lung cancer risk.

Note: Bunting is a measure of a person's long-term smoking. It is calculated by multiplying the number of packs smoked per day by the number of years that person has smoked. For example, 1 pack of years is equal to 1 pack per day for 1 year, or 2 packs per day for half a year, and so on.

Dr Jan Vijg, who led the study, said: "PBBCs can survive for years, even decades, and therefore accumulate mutations as they age and smoke. Of all lung cell types, lung epithelial cells are the most cancerous. The phenomenon of gene mutation inhibition in people who smoke a lot has pointed out a new direction for our research and development. Developing a novel assay that can measure an individual's ABILITY to repair or detoxify DNA may provide a new way to assess an individual's risk of lung cancer. ”

Organs that are harmful to smoking

The lungs bear the brunt of it

The China Report on the Health Hazards of Smoking states that smoking addiction is a chronic disease called tobacco dependence. Although not all smokers develop tobacco dependence, it is difficult for smokers to quit once they develop tobacco dependence, and long-term smoking is a huge harm to the lungs.

1

lung cancer

Tobacco contains more than 100 carcinogens and more than 70 in tobacco smoke [2]. Epidemiological studies have shown that the occurrence and development of lung cancer is the result of genetic and environmental interactions, of which smoking remains the largest risk factor. The WHO campaign for World No Tobacco Day mentions that about 1.2 million people die each year from lung cancer caused by smoking, and smokers are up to 22 times more likely to develop lung cancer than non-smokers [3].

Lung cancer in large part among non-smokers is due to long-term exposure to tobacco contamination. Non-smokers exposed to secondhand smoke at home or in the workplace had a 30 percent increased risk of developing lung cancer. More than 50 percent of women worldwide are exposed to environmental tobacco smoke (ETS), and the exposure dose response of the relationship between ETS and female lung cancer in both case-control and cohort studies suggests that high-dose exposure to ETS, especially to ETS for more than 20 years, is a major risk determinant of ETS leading to lung cancer in women [4].

2

Chronic respiratory diseases

Tobacco smoke is a toxic particle containing chemicals such as nicotine, which acts as an active oxidant, induces inflammation after reaching the gas exchange zone, has a genotoxic effect, induces activation of epithelial cells and endothelial cells, causes the secretion of inflammatory cytokines and chemokines, re-recruits immune cells to the pulmonary septal region including the small airways, pulmonary grand airways, and lung parenchyma, leads to the activation of macrophages and fibroblasts, and ultimately leads to interstitial fibrosis of the lungs, causing a series of chronic respiratory diseases [5].

Smoking is a major cause of chronic obstructive pulmonary disease, which refers to the accumulation of pus-filled mucus in the lungs, leading to painful coughs and difficulty breathing. Because tobacco smoke can significantly slow lung development, people who start smoking at a young age are particularly at high risk of COPD. Tobacco also exacerbates asthma, which limits activity and leads to disability. Quitting smoking as early as possible is the most effective treatment to slow the development of COPD and improve asthma symptoms.

3

pulmonary tuberculosis

Tuberculosis is a chronic infectious disease involving the respiratory system, and common clinical symptoms such as fever, cough, sputum production, fatigue, weight loss, dyspnea, chest pain, and hemoptysis can cause a decline in the quality of life and a decrease in social behavior. Smoking leads to mycobacterium tuberculosis infection, which is clearly associated with smoking years and smoking intensity. Exposure to secondhand smoke also increases the risk of conjugated Mycobacterium tuberculosis infection and the onset of tuberculosis.

The mechanism by which smoking increases the risk of Mycobacterium tuberculosis infection and tuberculosis is not clear, and some scholars believe that inhalation of smoke can cause damage to the cilia of respiratory epithelial cells, affecting the clearance of Mycobacterium tuberculosis by the respiratory system and leading to Mycobacterium tuberculosis infection. It may also be associated with cigarette smoke extracts causing bronchoalveolar inflammation and regulating the expression of immune molecules [6]. However, it is an indisputable fact that smoking will increase the infectivity of tuberculosis patients and increase the burden on society.

As we all know, smoking has a negative impact on health, but there are not a few people who have a fluke mentality and bet that they have "detoxification genes". Some people selectively ignore it, taking a small number of "survivors" as an example to explain the rationality of smoking, but ignoring more cases of losing health or even life because of smoking. Life is only a few decades, to quality, quantity or both, the choice is in your hands!

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Resources:

[1] Huang Z, Sun S, Lee M, et al. Single-cell analysis of somaticmutations in human bronchial epithelial cells in relation to aging and smoking. Nat Genet. 2022 Apr;54(4):492-498. doi: 10.1038/s41588-022-01035-w. Epub 2022Apr 11. PMID: 35410377.

Editorial Board of the Journal. Smoke-free life and healthy China[J].Chinese Journal of General Medicine,2022,20(03):374.

[4] Ni X, Xu N, Wang Q. Meta-Analysis and Systematic Review in Environmental Tobacco Smoke Risk of Female Lung Cancer by Research Type. Int J Environ Res Public Health. 2018 Jun27;15(7):1348. doi: 10.3390/ijerph15071348. PMID: 29954105; PMCID: PMC6068922.

[5] Checa M, Hagood JS, Velazquez-Cruz R, et al. Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells. PLoS One. 2016 Mar 2;11(3):e0150383. doi: 10.1371/journal.pone.0150383. PMID: 26934369; PMCID: PMC4775036.

[6] Gleeson LE, O'Leary SM, Ryan D, et al. Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium tuberculosis Infection. Am JRespir Cell Mol Biol. 2018 Nov;59(5):572-579. doi: 10.1165/rcmb.2018-0162OC.PMID: 29944387.

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