A prospective study of mitochondrial DNA copy number and the risk of prostate cancer

• Published in: Cancer causes & control Vol. 28; no. 6; pp. 529 - 538
• Main Authors: Moore, Amy, Lan, Qing, Hofmann, Jonathan N., Liu, Chin-San, Cheng, Wen-Ling, Lin, Ta-Tsung, Berndt, Sonja I.
• Format: Journal Article
• Language: English
• Published: Cham Springer Science + Business Media 01.06.2017; Springer International Publishing; Springer Nature B.V
• Subjects: Aged; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Case-Control Studies; DNA Copy Number Variations; DNA Damage; DNA, Mitochondrial; Epidemiology; Hematology; Humans; Leukocytes; Lung cancer; Male; Medical screening; Middle Aged; Mitochondrial DNA; Neoplasm Grading; Oncology; ORIGINAL PAPER; Ovarian cancer; Prospective Studies; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Public Health; Regression analysis; Risk Factors; United States > US; Prospective; Genetics; Mitochondrial DNA; Copy number; Prostate cancer; Risk factors
• ISSN: 0957-5243; 1573-7225
• DOI: 10.1007/s10552-017-0879-x

Purpose 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.