Mitochondrial DNA copy number in peripheral blood leukocytes and the aggressiveness of localized prostate cancer

Abstract

We investigated whether low mitochondrial DNA copy number (mtDNAcn) in peripheral blood leukocytes at diagnosis was associated with an increased risk of the aggressive form of the tumor and disease progression among localized prostate cancer (PCa) patients. We recruited 1,751 non-Hispanic white men with previously untreated PCa from The University of Texas MD Anderson Cancer Center. mtDNAcn was categorized into three groups according to tertiles. We used multivariate logistic regression to estimate the odds ratios (ORs) and 95 percent confidence intervals (95% CIs) for the association of mtDNAcn with the risk of having aggressive PCa at diagnosis. We used Cox proportional hazards model to estimate hazard ratios (HRs) and 95% CIs for disease progression. We observed an inverse association between aggressiveness of PCa and mtDNAcn (P < 0.001). In multivariate analysis, compared to patients in the highest tertile of mtDNAcn, those in the second and lowest tertiles had significantly increased risks of presenting with the high-risk form of PCa, as defined by the D’Amico criteria, with ORs of 1.33 (95% CI, 0.89–1.98; P = 0.17) and 1.53 (95% CI, 1.02–2.30; P = 0.04), respectively. Furthermore, PCa patients in the lowest and second tertiles combined relative to those in the highest tertile had a 56% increased risk of disease progression (HR, 1.56; 95% CI, 0.96–2.54; P = 0.07). In summary, our results suggested that low mtDNAcn in peripheral blood leukocytes was associated with aggressive PCa at diagnosis and might further predict poor progression-free survival among localized PCa patients.