According to researchers, when individuals quit smoking it not only stops further damage from accruing, but it also may lead to the reawakening of cells that were not damaged by tobacco carcinogens.
A study published in Nature found that by stopping smoking – at any age – individuals might not only slow the accumulation of further damage to their lungs but could also reawaken cells that have not been damaged by past lifestyle choices.1
“Epidemiological studies show that the health benefits of stopping smoking begin immediately, accrue with time since cessation, and are evident even after quitting late in life,” the authors wrote. “That these benefits could be facilitated by replenishment of the bronchial epithelium with cells that are essentially impervious to decades of sustained cigarette smoking attests to the resilience and regenerative capacity of the lungs.”
In this study, researchers sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 individuals who underwent a bronchoscopy for clinical indications. Tobacco smoking was found to be the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell. This massively increased the variance both within and between the subjects, generating several distinct mutational signatures of substitutions and of insertions and deletions.
A population of cells in those with a history of smoking had mutational burdens equivalent to those expected for individuals who had never smoked. These cells had a lesser amount of damage from tobacco-specific mutational processes, were four times more common in ex-smokers than those who currently smoked, and had remarkably longer telomeres than their more mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had 2 or even 3 drivers.
This data suggests that while tobacco smoking enhances mutational burden, cell-to-cell heterogeneity, and driver mutations, quitting supports replenishment of the bronchial epithelium from mitotically quiescent cells that have evaded tobacco mutagenesis.
“As expected, exposure to tobacco smoke increases the number of somatic mutations (by an average of a few thousand mutations per normal bronchial cell); the excess mutations are attributable to signatures of carcinogens in cigarette smoke; and the increased mutational burden generates more driver mutations,” the authors wrote. “What is unexpected, however, is the pronounced within-patient variation in mutational burden among smokers: cells from one small biopsy of bronchial epithelium can vary tenfold in their mutational burden, from 1,000 to over 10,000 mutations per cell.”
The researchers indicated that they still need to evaluate what portion of the lungs are repaired after individuals stop smoking.
According to the American Cancer Society, lung cancer is the second most common cancer in both men and women in the US.2 Lung cancer makes up almost 25% of all cancer deaths, and in 2020 alone, an estimated 135,720 deaths will result from lung cancer.
1. Yoshida K, Gowers K, Lee-Six H, et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature. doi:10.1038/s41586-020-1961-1.
2. American Cancer Society. Key Statistics for Lung Cancer. American Cancer Society website. Published January 8, 2020. cancer.org/content/cancer/en/cancer/lung-cancer/about/key-statistics.html. Accessed January 29, 2020.