Mitochondrial copy number and risk of breast cancer: a pilot study.
Mitochondrial copy number and risk of breast cancer: a pilot study.
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DOI：
10.1016/j.mito.2009.09.004
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发表时间：
2010-01
期刊：
影响因子：
4.4
通讯作者：
Zhao, Hua
中科院分区：
文献类型：
--
作者：
Shen, Jie;Platek, Mary;Mahasneh, Amjad;Ambrosone, Christine B.;Zhao, Hua
有人提出，每个细胞的线粒体 DNA (mtDNA) 拷贝数反映了未知遗传因素和影响氧化应激水平的暴露之间的基因-环境相互作用。然而，线粒体DNA的拷贝数是否可以作为与氧化应激相关的人类癌症（例如乳腺癌）的风险预测因子，仍有待确定。为了探讨 mtDNA 拷贝数在乳腺癌病因学中的作用，我们分析了 103 名乳腺癌患者和 103 名匹配对照受试者全血中的 mtDNA 拷贝数，并检查了其与内源性抗氧化剂的关系。乳腺癌病例患者的 mtDNA 拷贝数显着高于对照组（中位数：1.29 vs. 0.80，P < 0.01）。与低拷贝数（比值比 (OR) = 4.67，95% CI：2.45–8.92）相比，高 mtDNA 拷贝数（高于对照中位数）与乳腺癌风险统计显着增加相关，趋势分析中剂量反应关系具有统计学显着性（P < 0.01）。此外，在病例（总谷胱甘肽、CuZn-SOD 活性和髓过氧化物酶 (MPO)）或对照组（过氧化氢酶 (CAT) 活性）中，mtDNA 拷贝数与血液中几种重要的内源性氧化剂和抗氧化剂显着负相关。这些结果表明，线粒体 DNA 拷贝数可能与乳腺癌风险相关，可能是通过氧化应激机制实现的。
It has been proposed that the copy number of mitochondria DNA (mtDNA) per cell reflects gene–environment interactions between unknown hereditary factors and exposures affecting levels of oxidative stress. However, whether copy number of mtDNA could be a risk predictor of oxidative stress-related human cancers, such as breast cancer, remains to be determined. To explore the role of mtDNA copy number in breast cancer etiology, we analyzed mtDNA copy number in whole blood from 103 patients with breast cancer and 103 matched control subjects and examined in relation to endogenous antioxidants. Case patients with breast cancer had a statistically significantly higher mtDNA copy number than control subjects (median: 1.29 vs. 0.80, P < 0.01). High mtDNA copy number (above the median in controls) was associated with a statistically significantly increased risk of breast cancer, compared with low copy number (Odds ratio (OR) = 4.67, 95% CI: 2.45–8.92), with a statistically significant dose–response relationship in trend analysis (P < 0.01). Moreover, mtDNA copy number was significantly inversely associated with several important endogenous oxidants and antioxidants in blood in either the cases (total glutathione, CuZn-SOD activity and myeloperoxidase (MPO)) or the controls (catalase (CAT) activity). These results suggest the mtDNA copy number could be associated with risk of breast cancer, perhaps through an oxidative stress mechanism.
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