Mitochondrial DNA Content Increase in Response to Cigarette Smoking
- Brett G. Masayesva1,
- Elizabeth Mambo1,
- Rodney J. Taylor1,
- Olga G. Goloubeva4,
- Shaoyu Zhou1,
- Yoram Cohen1,
- Khalid Minhas1,
- Wayne Koch1,
- James Sciubba2,
- Anthony J. Alberg3,
- David Sidransky1 and
- Joseph Califano1
- 1Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division; 2Division of Dental and Oral Medicine; 3Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins Medical Institutions; and 4Department of Biostatistics, University of Maryland Health System, Baltimore, Maryland
- Requests for reprints:
Joseph Califano, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, 601 North Caroline Street, 6th Floor, Baltimore, MD 21287-0910. Phone: 410-502-5133; Fax: 410-955-8510. E-mail: jcalifa{at}jhmi.edu
Abstract
An increase in mitochondrial DNA (mtDNA) content and decline in mitochondrial function occurs with aging and in response to DNA-damaging agents, including tobacco smoke. We did a cross-sectional study and quantified changes in mtDNA content in a population of individuals with varied smoking and alcohol exposure. Age, smoking history, ethanol intake, and other demographic data were characterized for 604 individuals participating in a screening study for smoking-related upper aerodigestive malignancy. Total DNA was extracted from exfoliated cells in saliva. DNA from a nuclear gene, β-actin, and two mitochondrial genes, cytochrome c oxidase I and II (Cox I and Cox II), were quantified by real-time PCR. mtDNA content was correlated with age, exposure history, and other variables using multivariate regression analyses. A significant increase (P < 0.001) in mtDNA content was noted in smokers (31% and 29% increase for Cox I and Cox II, respectively) and former smokers (31% and 34%) when compared with never smokers. This association persisted after adjustment for other significant factors including age, alcohol drinking, and income (P < 0.001). Increased mtDNA content was positively associated with pack-years of smoking (P = 0.02). Despite an average smoking cessation interval of 21 years in former smokers, tobacco cessation interval was not statistically significantly associated with mtDNA content. Smoking is associated with increased mtDNA content in a dose-dependent fashion. Mitochondrial DNA alterations in response to smoking persist for several decades after smoking cessation, consistent with long-term, smoking-related damage. (Cancer Epidemiol Biomarkers Prev 2006;15(1):19–24)
Footnotes
-
Grant support: Maryland Cigarette Restitution Fund (J. Califano), National Institute of Dental and Craniofacial grant 1R01DE015939-01 (J. Califano), Damon Runyon Cancer Research Foundation grant CI-#9 (J. Califano), Flight Attendant Medical Research Institute's Clinical Innovator Award (J. Califano), and National Cancer Institute K07 award grant CA73790 (A.J. Alberg).
-
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
Note: J. Califano is a Damon Runyon-Lilly Clinical Investigator.
-
Supplementary data for this article are available at Cancer Epidemiology Biomarkers and Prevention Online (http://cebp.aacrjournals.org/).
-
- Accepted October 10, 2005.
- Received March 24, 2005.
- Revision received September 23, 2005.
