Thyagarajan Bharat, Guan Weihua, Fedirko Veronika, Barcelo Helene, Tu Huakang, Gross Myron, Goodman Michael, Bostick Roberd M
Department of Laboratory Medicine Pathology, Medical School University of Minnesota, Minneapolis, Minnesota.
Department of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
Mol Carcinog. 2016 Aug;55(8):1290-6. doi: 10.1002/mc.22370. Epub 2015 Aug 10.
Despite previously reported associations between peripheral blood mtDNA copy number and colorectal cancer, it remains unclear whether altered mtDNA copy number in peripheral blood is a risk factor for colorectal cancer or a biomarker for undiagnosed colorectal cancer. Though colorectal adenomas are well-recognized precursor lesions to colorectal cancer, no study has evaluated an association between mtDNA copy number and colorectal adenoma risk. Hence, we investigated an association between peripheral blood mtDNA copy number and incident, sporadic colorectal adenoma in 412 colorectal adenoma cases and 526 cancer-free controls pooled from three colonoscopy-based case-control studies that used identical methods for case ascertainment, risk factor determination, and biospecimen collection. We also evaluated associations between relative mtDNA copy number and markers of oxidative stress, including circulating F2 -isoprostanes, carotenoids, and fluorescent oxidation products. We measured mtDNA copy number using a quantitative real time polymerase chain reaction (PCR). We used unconditional logistic regression to analyze the association between mtDNA copy number and colorectal adenoma risk after multivariable adjustment. We found no association between logarithmically transformed relative mtDNA copy number, analyzed as a continuous variable, and colorectal adenoma risk (odds ratio = 1.02, 95%CI: 0.82-1.27; P = 0.86). There were no statistically significant associations between relative mtDNA copy number and other markers of oxidative stress. Our findings, taken together with those from previous studies, suggest that relative mtDNA copy number in peripheral blood may more likely be a marker of early colorectal cancer than of risk for the disease or of in vivo oxidative stress. © 2015 Wiley Periodicals, Inc.
尽管先前有报道称外周血线粒体DNA(mtDNA)拷贝数与结直肠癌之间存在关联,但外周血中mtDNA拷贝数的改变究竟是结直肠癌的危险因素还是未诊断出的结直肠癌的生物标志物仍不清楚。虽然结直肠腺瘤是公认的结直肠癌前体病变,但尚无研究评估mtDNA拷贝数与结直肠腺瘤风险之间的关联。因此,我们在412例结直肠腺瘤病例和526例无癌对照中调查了外周血mtDNA拷贝数与偶发性散发性结直肠腺瘤之间的关联,这些病例和对照来自三项基于结肠镜检查的病例对照研究,这些研究在病例确定、危险因素判定和生物样本采集方面采用了相同的方法。我们还评估了相对mtDNA拷贝数与氧化应激标志物之间的关联,包括循环F2 -异前列腺素、类胡萝卜素和荧光氧化产物。我们使用定量实时聚合酶链反应(PCR)测量mtDNA拷贝数。我们使用无条件逻辑回归分析多变量调整后mtDNA拷贝数与结直肠腺瘤风险之间的关联。我们发现,作为连续变量分析的对数转换后的相对mtDNA拷贝数与结直肠腺瘤风险之间无关联(优势比=1.02,95%置信区间:0.82 - 1.27;P = 0.86)。相对mtDNA拷贝数与其他氧化应激标志物之间无统计学显著关联。我们的研究结果与先前研究的结果共同表明,外周血中的相对mtDNA拷贝数更可能是早期结直肠癌的标志物,而非该疾病的风险标志物或体内氧化应激的标志物。© 2015威利期刊公司