There are more than 60 carcinogens in tobacco smoke that are known to directly mutate lung epithelial cell DNA. Therefore, it’s no surprise that 80-90% of lung cancer deaths can be attributed to exposure to tobacco smoke. Because smoking can be so harmful to human health, ad campaigns have been launched to stop young people from taking up the habit and encourage people to quit smoking. However, the data on how much cessation of smoking decreases the risk of lung cancer is pretty tricky.
An article published at the end of January 2020 looked at the somatic mutations that tobacco smoking causes in human bronchi (Yoshida et al. 2020). The paper cites previous data that says if you stop smoking by middle age or earlier, much of the risk of tobacco-associated lung cancer can be avoided. The longer it has been since someone stopped smoking, the higher the likelihood that they will avoid cancer. This research team set out to find a mechanistic reason why stopping smoking almost always reduces the risk of health effects by looking at the mutation burdens of cells in patients who had undergone bronchoscopies.
As expected, there were higher levels of mutations in cells that had been exposed to tobacco smoke. What was unexpected was that there were huge variations in the number of mutations in cells recovered from very small biopsy areas. Some of the cells recovered had 10,000 mutations, which is typical in cells with tobacco exposure, but a lot of the cells had so few mutations that they were equivalent to the cells of never-smokers. The researchers did an analysis of telomere length of these cells to see how many cell divisions they had undergone, and found that the cells with low mutation levels had long telomeres. This suggests that they are relatively new cells that are potentially recent descendants of quiescent stem cells. These cell populations also expand after cessation of smoking. The researchers do not have a definitive reason for why these cells expand after you stop smoking or how exactly these cells avoid damage.
Whatever the mechanism, the take-home message is clear: it is never too late to stop smoking. Health benefits of stopping smoking begin immediately, build up as more and more time passes without smoking, and are relevant even if you stop smoking late in life.
Yoshida, K., Gowers, K. H. C., Lee-Six, H., Chandrasekharan, D. P., Coorens, T., Maughan, E. F., Beal, K., Menzies, A., Millar, F. R., Anderson, E., Clarke, S. E., Pennycuick, A., Thakrar, R. M., Butler, C. R., Kakiuchi, N., Hirano, T., Hynds, R. E., Stratton, M. R., Martincorena, I., … Campbell, P. J. (2020). Tobacco smoking and somatic mutations in human bronchial epithelium. Nature, 578(7794), 266–272. https://doi.org/10.1038/s41586-020-1961-1
Working in a heart clinic we are constantly encouraging cessation of smoking but it is a very disheartening occasion when a patient says no. Some people find it in themselves immdiately after something bad happens to stop smoking but the truth is waiting for something bad to happen to stop smoking is a pretty bad plan. It looks like even quitting at age 65 can extend overall life expectancy by 2 years, which is a lot of time. The paper also found that stopping before age 35 pretty much removed any effect of smoking on life expectancy (Taylor et. al., 2002). This seems to correlate with the data found in your paper. Plus your point about the longer you smoke the more likely you are to have mutations makes sense. Just because one cigarette didn't mutate your cells and give you cancer doesn't mean the next one won't.
ReplyDeleteTaylor, D. H., Jr, Hasselblad, V., Henley, S. J., Thun, M. J., & Sloan, F. A. (2002). Benefits of smoking cessation for longevity. American journal of public health, 92(6), 990–996. https://doi.org/10.2105/ajph.92.6.990
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ReplyDeleteHi Moriah, this is a great topic to discuss as I have seen many patients with cardiovascular disease and other comorbidities who are smokers. It is indeed disheartening to see a patient in pain due to compromised health, though they are not able to quit smoking due to nicotine content. In regard to whether or not it is too late to quit smoking and the various effects that it can have on the airway, a 2009 study looked at cilia damage in human airway epithelium. When comparing the cilia length in normal nonsmokers and smokers, analysis of the individual lengths of cilia were reduced by 13% compared to the nonsmokers, in addition to 6 cilia-related genes whose expression was significantly reduced in healthy smokers compared to healthy nonsmokers (Leopold et al., 2009). With shortened cilia due to carcinogenic damage, and based on the Leopold et al. study, I imagine that though it may never be too late for smokers to stop exacerbating the condition, it would be difficult to reverse the pathogenesis of smoking-induced lung disease. And I agree with you and Chase that even if one cigarette will not cause as much damage, it does not mean that the next ones will not, especially when they are dosed with addictive chemicals.
ReplyDeleteLeopold, P. L., O'Mahony, M. J., Lian, X. J., Tilley, A. E., Harvey, B. G., & Crystal, R. G. (2009). Smoking is associated with shortened airway cilia. PloS one, 4(12), e8157. https://doi.org/10.1371/journal.pone.0008157