Increased mitochondrial DNA content in saliva associated with head and neck cancer.
Alterations of the mitochondrial DNA (mtDNA) have been described in human tumors and in other tissues in association with smoking exposure. We did quantitative PCR of cytochrome c oxidase I (Cox I) and cytochrome c oxidase II (Cox II) genes on oral rinse samples obtained from 94 patients with primary head and neck squamous cell carcinoma (HNSC) and a control group of 656 subjects. Mitochondrial DNA/nuclear DNA in saliva from HNSC patients and controls in relationship to smoking exposure, ethanol intake, and tumor stage were examined. Mean levels of Cox I and Cox II in saliva samples were significantly higher in HNSC patients: Cox I, 0.076 [95% confidence interval (95% CI), 0.06-0.09] and Cox II, 0.055 (95% CI, 0.04-0.07) in comparison with controls Cox I, 0.054 (95% CI, 0.05-0.06), P < 0.0001 and Cox II, 0.046 (95% CI, 0.04-0.05), P = 0.003 (t test). MtDNA levels were elevated in primary tumors when compared with matched, pretreatment saliva and significant correlation was noted (Cox I, r = 0.30, P = 0.005 and Cox II r = 0.33, P = 0.002, respectively, Pearson's correlation). On univariate analysis, smoking, age, HNSC diagnosis, and advanced stage of HNSC were associated with higher level of mtDNA content in saliva. Multivariate analysis showed a significant and independent association of HNSC diagnosis, age, and smoking with increasing mtDNA/nuclear DNA for Cox I and Cox II. mtDNA content alteration is associated with HNSC independently of age and smoking exposure, can be detected in saliva, and may be due to elevation in mtDNA content in primary HNSC.
Jiang
Wei-Wen
WW
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Division, Baltimore, MD 21287-0910, USA.
Masayesva
Brett
B
Zahurak
Marianna
M
Carvalho
Andre Lopes
AL
Rosenbaum
Eli
E
Mambo
Elizabeth
E
Zhou
Shaoyu
S
Minhas
Khalid
K
Benoit
Nicole
N
Westra
William H
WH
Alberg
Anthony
A
Sidransky
David
D
Koch
Wayne
W
Califano
Joseph
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012463:Saliva / Q000378:metabolism*
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV