Abstract
BackgroundLow mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U.S. population-based case-control study of RCC.Methodology/Principal FindingsRelative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay using DNA extracted from peripheral whole blood. Cases (n = 603) had significantly lower mtDNA copy number than controls (n = 603; medians 0.85, 0.91 respectively; P = 0.0001). In multiple logistic regression analyses, the lowest quartile of mtDNA copy number was associated with a 60% increase in RCC risk relative to the highest quartile (OR = 1.6, 95% CI = 1.1–2.2; P trend = 0.009). This association remained in analyses restricted to cases treated by surgery alone (OR Q1 = 1.4, 95% CI = 1.0–2.1) and to localized tumors (2.0, 1.3–2.8).Conclusions/SignificanceOur findings from this investigation, to our knowledge the largest of its kind, offer important confirmatory evidence that low mtDNA copy number is associated with increased RCC risk. Additional research is needed to assess whether the association is replicable in prospective studies.
Highlights
Mitochondria, the primary source of energy for eukaryotic cells, play an important role in other cellular activities such as calcium regulation and apoptosis, and are a major target and source of reactive oxygen species [1]
Decreasing mitochondrial DNA (mtDNA) copy number was associated with increased renal cell carcinoma (RCC) risk
The lowest quartile of mtDNA copy number (Q1) was associated with a 60% increase in RCC risk relative to the highest quartile (ORQ1 = 1.6, 95% CI = 1.1–2.2)
Summary
Mitochondria, the primary source of energy for eukaryotic cells, play an important role in other cellular activities such as calcium regulation and apoptosis, and are a major target and source of reactive oxygen species [1]. Investigations of two case series of RCC detected reduced mtDNA content in tumor tissue relative to adjacent normal tissue [3,4]. These findings suggest that mechanisms associated with altered mtDNA copy number may contribute to RCC development. Low mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U.S population-based case-control study of RCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
