An association analysis between mitochondrial DNA content, G10398A polymorphism, HPV infection, and the prognosis of cervical cancer in the Chinese Han population

Tumour Biol. 2016 Apr;37(4):5599-607. doi: 10.1007/s13277-015-4429-4. Epub 2015 Nov 14.

Abstract

The aim was to analyze quantitative (mitochondrial DNA (mtDNA) content) and qualitative (G10398A polymorphism) mtDNA alterations as well as human papillomavirus (HPV) infection in cervical cancer prognosis. One hundred and twenty-two cases of formalin-fixed paraffin-embedded cervical carcinoma specimens were collected from the Yichang Tumor Hospital and Zhongnan Hospital of Wuhan University in the recent 10 years together with medical records. A quantitative real-time PCR (RT-PCR) was used to determine the copy number of the mitochondrial DNA and HPV expression levels. G10398A polymorphism was determined by PCR-RFLP assay. The overall survival of patients with higher mtDNA content was significantly reduced compared with lower mtDNA content patients (P = 0.029). But there was no difference of prognosis between the mtDNA 10398 A allele and G allele. However, the Kaplan-Meier survival curve illustrated a significantly reduced overall survival in the patients with 10398A plus high mtDNA copy number compared with the other groups (P < 0.05). Although no association between HPV expression level and cervical cancer prognosis was observed, 10398A got increased mtDNA content compared with 10398G (P < 0.05) and 10398G displayed an increased HPV-positive rate compared with 10398A. Furthermore, HPV-18 and mtDNA content were positively related in the younger subgroup (≤45 years) (correlation coefficient = 0.456, P = 0.022). This study indicated that mtDNA content and HPV infection status are associated with cervical cancer prognosis. High mitochondrial DNA content plus 10398 A may be a marker of poor prognosis in cervical cancer. And mtDNA variation may potentially influence the predisposition to HPV infection and cervical carcinogenesis.

Keywords: 10398 site; Cervical cancer; HPV; Mitochondrial DNA content; Prognosis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / isolation & purification
  • Female
  • Genotype
  • Human papillomavirus 18 / genetics
  • Human papillomavirus 18 / pathogenicity
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis*
  • Risk Factors
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • DNA, Mitochondrial