title: A prospective study of mitochondrial DNA copy number and the risk of prostate cancer.
abstract: OBJECTIVE
  Evidence suggests that mitochondrial DNA (mtDNA) copy number increases in response to DNA damage. Increased mtDNA copy number has been observed in prostate cancer (PCa) cells, suggesting a role in PCa development, but this association has not yet been investigated prospectively.
  
  
  METHODS
  We conducted a nested case-control study (793 cases and 790 controls) of men randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) to evaluate the association between pre-diagnosis mtDNA copy number, measured in peripheral blood leukocytes, and the risk of PCa. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and polytomous logistic regression to analyze differences in associations by non-aggressive (Stage I/II AND Gleason grade < 8) or aggressive (Stage III/IV OR Gleason grade ≥ 8) PCa.
  
  
  RESULTS
  Although mtDNA copy number was not significantly associated with PCa risk overall (OR 1.23, 95% CI 0.97-1.55, p = 0.089), increasing mtDNA copy number was associated with an increased risk of non-aggressive PCa (OR 1.29, 95% CI 1.01-1.65, p = 0.044) compared to controls. No association was observed with aggressive PCa (OR 1.02, 95% CI 0.64-1.63, p = 0.933). Higher mtDNA copy number was also associated with increased PSA levels among controls (p = 0.014).
  
  
  CONCLUSIONS
  These results suggest that alterations in mtDNA copy number may reflect disruption of the normal prostate glandular architecture seen in early-stage disease, as opposed to reflecting the large number of tumor cells seen with advanced PCa.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. amy.moore@nih.gov.
authors.forename: Amy
authors.initials: A
authors.lastname: Moore
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Hofmann
authors.affiliation: Vascular and Genomic Research Center, Changhua Christian Hospital, 7F No. 235, Syuguang Rd., Changhua, 500, Taiwan.
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.affiliation: Vascular and Genomic Research Center, Changhua Christian Hospital, 7F No. 235, Syuguang Rd., Changhua, 500, Taiwan.
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Cheng
authors.affiliation: Vascular and Genomic Research Center, Changhua Christian Hospital, 7F No. 235, Syuguang Rd., Changhua, 500, Taiwan.
authors.forename: Ta-Tsung
authors.initials: TT
authors.lastname: Lin
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004249:DNA Damage; D004272:DNA, Mitochondrial; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial
keywords: Copy number; Genetics; Mitochondrial DNA; Prospective; Prostate cancer; Risk factors