Association of leukocyte mitochondrial DNA copy number with colorectal cancer risk: Results from the Shanghai Women's Health Study.
Association of leukocyte mitochondrial DNA copy number with colorectal cancer risk: Results from the Shanghai Women's Health Study.
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DOI：
10.1158/1055-9965.epi-14-0297
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Cai Q
中科院分区：
文献类型：
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作者：
Huang B;Gao YT;Shu XO;Wen W;Yang G;Li G;Courtney R;Ji BT;Li HL;Purdue MP;Zheng W;Cai Q
线粒体在细胞能量代谢、自由基产生、细胞凋亡等过程中发挥重要作用，可能参与肿瘤的发生发展。我们在一项病例对照研究中评估了外周血白细胞线粒体DNA拷贝数与结直肠癌风险的关系，该研究嵌套在上海妇女健康研究中，该研究嵌套在444例结直肠癌病例和1423例对照中。在癌症诊断之前，通过使用在研究登记时收集的外周血白细胞DNA样本的实时定量聚合酶链式反应测定相对mtDNA拷贝数。我们发现，在随后发生结直肠癌的妇女中，mtDNA基准线拷贝数(几何平均数=0.277，95%可信区间：0.269-0.285)低于未患癌的妇女(几何平均数=0.288，95%可信区间：0.284-0.293；P=0.0153)。与线粒体DNA拷贝数最高的三分位数(P=0.0204)相比，线粒体DNA拷贝数中、下三分位数的多变量调整优势比分别为1.2 6(95%CI：0.93~1.70)和1.44(95%CI：1.0 6~1.94)。这种联系几乎不受采血和癌症诊断之间的时间间隔的影响。我们的数据表明，外周血白细胞中mtDNA拷贝数可能是一种潜在的有助于结直肠癌风险评估的生物标志物。如果得到证实，在外周血白细胞中测量的mtDNA拷贝数可能是一个有助于结直肠癌风险评估的生物标志物。
Mitochondria play an important role in cellular energy metabolism, free radical production, and apoptosis and thus may be involved in cancer development. We evaluated mtDNA copy number in peripheral leukocytes in relation to CRC risk in a case-control study of 444 CRC cases and 1,423 controls nested in the Shanghai Women's Health Study, a population-based, prospective cohort study. Relative mtDNA copy number was determined by a quantitative real-time PCR assay using peripheral leukocyte DNA samples collected at the time of study enrollment, prior to cancer diagnosis. We found that baseline mtDNA copy number was lower among women who subsequently developed CRC (geometric mean = 0.277, 95% CI: 0.269-0.285) than among women who remained cancer-free (geometric mean = 0.288, 95% CI: 0.284-0.293; P=0.0153). Multivariate adjusted odds ratios (ORs) were 1.26 (95% CI: 0.93-1.70) and 1.44 (95% CI: 1.06-1.94) for the middle and lower tertiles of mtDNA copy number, respectively, compared with the upper tertile (highest mtDNA copy number; P for trend=0.0204). The association varied little by the interval between blood collection and cancer diagnosis. Our data suggest that mtDNA copy number measured in peripheral leukocytes may be a potential biomarker useful for CRC risk assessment. If confirmed, mtDNA copy number measured in peripheral leukocytes may be a biomarker useful for colorectal cancer risk assessment.