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Smoking-associated mitochondrial DNA mutations in human hair follicles
1Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Abstract:
The mitochondrial DNA (mtDNA) of hair follicles was used for studying the genotoxicity of smoking-mediated carcinogens. We determined the incidences of the 4,977 bp and 7,436 bp mtDNA deletions, tandem duplication in the D-loop region and the proportion of the 4,977 bp deleted mtDNA (dmtDNA) in the total DNA of hair follicles from 213 male non-smokers and 74 male smokers, respectively. Twenty-three patients with lung cancer were also investigated. We found that the current cigarette smokers had a 3.1 times higher average incidence of the 4,977 bp dmtDNA (RR: 3.1, P < 0.001) as compared with non-smokers, and this mtDNA deletion was especially prevalent in the old heavy smokers. For the smokers of the age above 70, the average incidence of the 4,977 bp dmtDNA was 3.7 times higher in the group with a smoking index of 401-800 (RR: 3.7, P < 0.005) and 3.2 times higher in the group with a smoking index greater than 800 (RR: 3.2, P < 0.005). However, there was no statistically significant relationship between the incidence of the 7,436 bp dmtDNA and the smoking index, although there was a mild increase in the percentage of the 7,436 bp dmtDNA with the increase of the consumption of cigarettes. No tandem duplication of mtDNA in the D-loop region was disclosed in either smokers or non-smokers group. The proportions of the 4,977 bp dmtDNA in hair follicles were found to correlate with age, but did not keep increasing with cigarette consumption except in the group of subjects with a smoking index of less than 400. On the other hand, we found that the average proportion of the 4,977 bp dmtDNA in the hair follicles was 1.201 +/- 0.371% for the patients with lung cancer who had a smoking index greater than 400, while that was only 0.146% for the age-matched healthy smokers with the same smoking index. In conclusion, the high incidence of the 4,977 bp dmtDNA of hair follicles is not only associated with aging but also correlated with the amount of cigarette smoking. A high proportion of the 4,977 bp dmtDNA in the hair follicles may be considered one of the molecular events that are associated with the occurrence of smoking-associated cancers.
Insights
Smoking significantly increases the 4,977 bp mitochondrial DNA deletion in hair follicles, a marker linked to aging and smoking-associated cancers. This finding highlights mtDNA deletions as potential biomarkers for smoking-related health risks.
Area of Science:
- Genetics
- Toxicology
- Oncology
Background:
- Smoking is a major cause of cancer.
- Mitochondrial DNA (mtDNA) deletions are associated with aging and disease.
- Hair follicles can serve as a non-invasive tissue for genotoxicity studies.
Purpose of the Study:
- To investigate the genotoxicity of smoking-mediated carcinogens using mitochondrial DNA (mtDNA) deletions in hair follicles.
- To determine the association between smoking habits and specific mtDNA deletions (4,977 bp and 7,436 bp) and tandem duplications.
- To evaluate the potential of mtDNA deletions as biomarkers for smoking-associated cancers, particularly lung cancer.
Main Methods:
- Analysis of mtDNA deletions (4,977 bp and 7,436 bp) and D-loop tandem duplications in hair follicles.
- Comparison of mtDNA deletion incidences between male non-smokers, smokers, and lung cancer patients.
- Correlation analysis of mtDNA deletion proportions with age and smoking index (cigarettes per day x years smoked).
Main Results:
- Current smokers exhibited a 3.1-fold higher incidence of the 4,977 bp mtDNA deletion compared to non-smokers.
- The 4,977 bp mtDNA deletion was more prevalent in older, heavy smokers, with increased incidence correlating with higher smoking indices.
- Lung cancer patients with a high smoking index showed significantly higher proportions of the 4,977 bp mtDNA deletion in hair follicles compared to age-matched healthy smokers.
Conclusions:
- The 4,977 bp mtDNA deletion in hair follicles is associated with both aging and the cumulative dose of cigarette smoking.
- A high proportion of the 4,977 bp mtDNA deletion may serve as a molecular marker for smoking-associated cancers.
- Further research into mtDNA deletions could lead to improved biomarkers for early cancer detection in smokers.