Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Cancer. 2011 Jul 15;117(14):3148-55. doi: 10.1002/cncr.25906. Epub 2011 Jan 18.
Compelling epidemiological evidence indicated that alterations of mitochondrial DNA (mtDNA), including mutations and abnormal content of mtDNA, were implicated in the tumorigenesis of several malignancies in a tumor-specific manner, such as lung cancer, breast cancer, and non-Hodgkin lymphoma. This study was undertaken to investigate whether mtDNA content in peripheral blood lymphocytes (PBLs) could be used as a risk predictor for colorectal cancer (CRC).
The mtDNA content was measured by using quantitative real-time polymerase chain reaction in PBLs from 320 CRC patients and 320 matched controls.
The authors found that CRC patients exhibited statistically significantly higher mtDNA content than matched controls (median, 1.03 vs .86; P < .001). They further assessed the association between mtDNA content and CRC risk using multivariate logistic regression. By using the median value in controls as the cutoff point, they found that, compared with low mtDNA content, high mtDNA content was associated with a significantly increased CRC risk (adjusted odds ratio, 2.03; 95% confidence interval, 1.41-2.81). In a trend analysis, they found a statistically significant dose-response relationship between higher mtDNA content and increased CRC risk (P for trend <.001). Stratified analysis showed that the association between mtDNA content and CRC risk was not modulated by major host characteristics.
These findings provide the first epidemiological evidence linking the high mtDNA content in PBLs to elevated CRC risk.
大量的流行病学证据表明，线粒体 DNA（mtDNA）的改变，包括突变和 mtDNA 的异常含量，与几种恶性肿瘤的肿瘤发生有关，如肺癌、乳腺癌和非霍奇金淋巴瘤。本研究旨在探讨外周血淋巴细胞（PBLs）中的 mtDNA 含量是否可以作为结直肠癌（CRC）的风险预测因子。
采用实时定量聚合酶链反应（PCR）法检测 320 例 CRC 患者和 320 例匹配对照者 PBLs 中的 mtDNA 含量。
作者发现 CRC 患者的 mtDNA 含量明显高于匹配对照组（中位数，1.03 vs.86；P<0.001）。他们进一步使用多变量逻辑回归评估了 mtDNA 含量与 CRC 风险之间的关联。以对照组的中位数为截断点，发现与低 mtDNA 含量相比，高 mtDNA 含量与 CRC 风险显著增加相关（调整后的比值比，2.03；95%置信区间，1.41-2.81）。在趋势分析中，他们发现 mtDNA 含量与 CRC 风险之间存在统计学显著的剂量-反应关系（趋势检验 P<.001）。分层分析显示，mtDNA 含量与 CRC 风险之间的关联不受主要宿主特征的调节。
这些发现提供了首个流行病学证据，表明 PBLs 中的高 mtDNA 含量与 CRC 风险升高有关。
