Mitochondrial DNA copy number in peripheral blood leukocytes is associated with biochemical recurrence in prostate cancer patients in African Americans

Carcinogenesis. 2020 May 14;41(3):267-273. doi: 10.1093/carcin/bgz139.

Abstract

Mitochondria play multiple important cellular functions. The purpose of this study was to evaluate whether leukocyte mitochondrial DNA copy number (mtDNAcn) is associated with aggressive prostate cancer (PCa) in African American (AA) men. We measured the mtDNAcn in peripheral blood leukocytes from 317 localized AA PCa patients and evaluated its associations with aggressive disease features at diagnosis and biochemical recurrence (BCR) after treatments. There was no significant difference in mtDNAcn among the clinical features at diagnosis, including age, prostate-specific antigen level, Gleason score and clinical stage under analysis of variance test. However, mtDNAcn was significantly associated with BCR in multivariate Cox analysis. Dichotomized into low and high mtDNAcn groups by the median value of mtDNAcn, patients with low mtDNAcn exhibited a significantly lower risk of BCR (hazard ratio = 0.32, 95% confidence interval: 0.13-0.79) compared to those with high mtDNAcn. There was a significant dose-response in tertile and quartile analyses (P for trend = 0.012 and 0.002, respectively). In Kaplan-Meier survival analyses, patients with higher mtDNAcn exhibited significantly shorter BCR-free survival time than those with lower mtDNAcn in dichotomous, tertile and quartile analyses, with long-rank P values of 0.017, 0.024 and 0.019, respectively. Our results showed for the first time that high leukocyte mtDNAcn was associated with worse prognosis in AA PCa patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics
  • Aged
  • DNA Copy Number Variations / genetics
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • Disease-Free Survival
  • Humans
  • Kaplan-Meier Estimate
  • Leukocytes / pathology
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Prostate / metabolism
  • Prostate / pathology
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • DNA, Mitochondrial
  • Prostate-Specific Antigen