Association Of Mitochondrial DNA Copy Number In Peripheral Blood Leukocytes With Risk And Prognosis Of Prostate Cancer

Objective:To investigate the relationship between mitochondrial DNA (mtDNA) copy number in peripheral blood leukocytes (PBLs) and the risk and the prognosis of prostate cancer (PCa).Methods:In a case-control study of196PCa patients and196age-paired normal controls, the association between mtDNA copy number in PBLs and PCa risk was evaluated. The relative mtDNA copy number was measured by using real-time PCR. Among the case cohort,89patients were subject to follow-up. Two endpoints i.e. progression-free survival (PFS) and overall survival (OS), were selected to evaluate the association between the prognosis of PCa and the mtDNA copy number.Results:PCa patients had significantly higher mtDNA copy numbers than controls (medians0.91and0.82, respectively; P<0.001). High mtDNA copy number was also associated with an increased risk of PCa (highest quartile vs lowest:odds ratio=2.52,95%confidence intervals:1.35-4.70;Ptrend=0.011). Patients with higher AJCC stage and Gleason score tended to have higher mtDNA copy numbers (P=0.002and P=0.012, respectively). Cox univariate and multivariate survival analysis indicated that mtDNA copy number was an effective predictor of PFS and OS. The Kaplan-Meier survival curves revealed that high mtDNA copy number was associated with poor PFS and OS in patients with PCa (P=0.007and P<0.001, respectively).Conclusions:Our findings provide the first evidence that increased mtDNA copy number in PBLs is significantly associated with an increased risk of PCa and, similarly, a poor prognosis in PCa patients. Quantification of mtDNA copy number in PBLs could be helpful to diagnosis and prognosis of PCa.