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PLoS By Category | Recent PLoS Articles
Hematology - Oncology - Public Health and Epidemiology - Biochemistry

A Case-Control Study of Peripheral Blood Mitochondrial DNA Copy Number and Risk of Renal Cell Carcinoma
Published: Friday, August 24, 2012
Author: Mark P. Purdue et al.

by Mark P. Purdue, Jonathan N. Hofmann, Joanne S. Colt, Mirjam Hoxha, Julie J. Ruterbusch, Faith G. Davis, Nathaniel Rothman, Sholom Wacholder, Kendra L. Schwartz, Andrea Baccarelli, Wong-Ho Chow

Background

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.

Methodology/Principal Findings

Relative 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; Ptrend?=?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/Significance

Our 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.

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