Peripheral Blood Mitochondrial DNA Copy Number Is Associated with Prostate Cancer Risk and Tumor Burden

Abstract

Alterations of mitochondrial DNA (mtDNA) have been associated with the risk of a number of human cancers; however, the relationship between mtDNA copy number in peripheral blood leukocytes (PBLs) and the risk of prostate cancer (PCa) has not been investigated. In a case-control study of 196 PCa patients and 196 age-paired healthy controls in a Chinese Han population, the association between mtDNA copy number in PBLs and PCa risk was evaluated. The relative mtDNA copy number was measured using quantitative real-time PCR; samples from three cases and two controls could not be assayed, leaving 193 cases and 194 controls for analysis. PCa patients had significantly higher mtDNA copy numbers than controls (medians 0.91 and 0.82, respectively; P<0.001). Dichotomized at the median value of mtDNA copy number in the controls, high mtDNA copy number was significantly associated with an increased risk of PCa (adjusted odds ratio = 1.85, 95% confidence interval: 1.21–2.83). A significant dose-response relationship was observed between mtDNA copy number and risk of PCa in quartile analysis (P trend = 0.011). Clinicopathological analysis showed that high mtDNA copy numbers in PCa patients were significantly associated with high Gleason score and advanced tumor stage, but not serum prostate-specific antigen level (P = 0.002, 0.012 and 0.544, respectively). These findings of the present study indicate that increased mtDNA copy number in PBLs is significantly associated with an increased risk of PCa and may be a reflection of tumor burden.

Elevated mitochondrial DNA copy numbers in pediatric acute lymphoblastic leukemia: A potential biomarker for predicting inferior survival

“…The same risk was, however, not observed in lung cancer across three prospective study populations from Europe, Asia, and the United States assessed by the same team of researchers . Increased mitochondrial DNA copy numbers in subjects compared with controls were also observed in a study on prostate cancer patients . This finding indicates that regulation of mitochondrial DNA copy number may follow different patterns in solid tumors compared with hematological malignancies.…”

“…22 Increased mitochondrial DNA copy numbers in subjects compared with controls were also observed in a study on prostate cancer patients. 23 Log-rank analysis was performed to compare the two groups: (C) EFS was significantly increased (P-value = 0.04) in patients (n = 25) with mitochondrial DNA copy numbers less than the median (77.4% survival) compared with patients (n = 26) with copy numbers greater than the median mitochondrial DNA copy number (42.2% survival). (D) OS was not significantly different between the two groups (Pvalue = 0.1175) with 82.2% and 62.7% survival in patients with less than and greater than the median mitochondrial DNA copy number, respectively…”

Cell-free mitochondrial DNA copy number variation in head and neck squamous cell carcinoma: A study of non-invasive biomarker from Northeast India

“…38 Increased mtDNA copy number is also an indication of lower levels of antioxidants in blood. 44 This highlights the consumption of antioxidant-rich foods such as green leafy vegetables and fruits may help in reducing the oxidative stress caused by tobacco-associated products 48,49 which are usually lacking in their diet. 31 The burden of HNSCC can be minimized by addressing common risk factors, which includes smoking, consumption of tobacco-related products and intake of alcohol.…”

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer

“…The role of increased mtDNA content in peripheral blood has been debated. While a possible association with PCa risk (adjusted odds ratio = 1.85, 95% confidence interval: 1.21-2.83) and worse pathology has been suggested, 14 others reported an association with non-aggressive PCa presentation (OR 1.29, 95% CI 1.01-1.65, P = 0.044). 15 Inversely, a low mtDNA copy number was associated with worse pathology and increased risk of PCa progression (HR, 1.56; 95% CI, 0.96-2.54; P = 0.07).…”