Tobacco smoking and somatic mutations in human bronchial epithelium.
Level 4 - case-series / case-control
Observational cross-sectional human tissue genomic study
PubMed 31996850 · doi:10.1038/s41586-020-1961-1
What was done
Whole-genome sequencing was conducted on 632 colonies derived from single bronchial epithelial cells sampled from 16 human subjects across never-smokers, ex-smokers, and current smokers to evaluate somatic mutational burdens, mutational signatures, driver mutations, and telomere lengths.
What was found
Tobacco smoking typically added 1,000 to 10,000 mutations per cell, increasing mutational variance and introducing distinct substitution and insertion/deletion signatures. Driver mutations affected 4% to 14% of cells in middle-aged never-smokers, compared to at least 25% of cells in current smokers (with 0% to 6% having two or three driver mutations). Ex-smokers harbored a population of bronchial cells with baseline mutational burdens and longer telomeres that was fourfold more frequent than in current smokers.
Why it matters
This study demonstrates that smoking inflicts pervasive genomic damage and cancer driver mutations throughout morphologically normal bronchial tissue, while showing that smoking cessation allows a reservoir of relatively undamaged cells to replenish the airway lining.
Limits
The study evaluated a very small human cohort of 16 participants. Growing single cells into colonies ex vivo was required for whole-genome sequencing, which may introduce culture selection biases. Detailed participant characteristics (such as pack-years and precise cessation duration) are omitted from the abstract.
Cited by
- supports Smoking causes chemicals to enter the lungs that induce DNA damage and increase the accumulation of genetic mutations.
- supports Cigarette smoke contains chemical carcinogens that directly damage the genome and cause genetic mutations.