Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America.
PLoS One. 2012;7(8):e43149. doi: 10.1371/journal.pone.0043149. Epub 2012 Aug 24.
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; 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/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.
低线粒体 DNA（mtDNA）拷贝数是肾细胞癌（RCC）的一个常见特征，可能影响肿瘤的发展。最近的一项病例对照研究结果表明，外周血中低 mtDNA 拷贝数可能是 RCC 风险增加的标志物。为了验证这一发现，我们测量了美国人群基于病例对照研究的 RCC 外周血 DNA 中的 mtDNA 拷贝数。
方法/主要发现：使用定量实时 PCR 检测法，通过从外周全血中提取的 DNA，重复测量了相对 mtDNA 拷贝数。病例组（n=603）的 mtDNA 拷贝数明显低于对照组（n=603；中位数分别为 0.85、0.91；P=0.0001）。在多因素逻辑回归分析中，与最高四分位组相比，最低四分位组的 mtDNA 拷贝数与 RCC 风险增加 60%相关（OR=1.6，95%CI=1.1-2.2；P（趋势）=0.009）。在仅接受手术治疗的病例分析中（OR（Q1）=1.4，95%CI=1.0-2.1）和局部肿瘤分析中（2.0，1.3-2.8），这种相关性仍然存在。
结论/意义：我们的研究结果提供了重要的证实性证据，表明低 mtDNA 拷贝数与 RCC 风险增加相关，这是对此类研究中最大规模的一项调查。需要进一步的研究来评估该相关性在前瞻性研究中是否具有可重复性。
