Kumar Bhupender, Bhat Zafar Iqbal, Bansal Savita, Saini Sunil, Naseem Afreen, Wahabi Khushnuma, Burman Archana, Kumar Geeta Trilok, Saluja Sundeep Singh, Rizvi M Moshahid Alam
1 Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi, India.
2 Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Tumour Biol. 2017 Nov;39(11):1010428317740296. doi: 10.1177/1010428317740296.
Globally, colorectal cancer is the third most common type of cancer. Genetic instability leading to cancer development is one of the major causes for development of cancer. Alterations in mitochondrial genome, that is, mutations, single-nucleotide polymorphisms, and copy number variations are known to contribute in cancer development. The aim of our study was to investigate association of mitochondrial T16189C polymorphism and copy number variation with colorectal cancer in North Indian population. DNA isolated from peripheral blood of 126 colorectal cancer patients and 114 healthy North Indian subjects was analyzed for T16189C polymorphism and half of them for mitochondrial copy number variation. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism, and copy number variation was estimated using real-time polymerase chain reaction, numbers of mitochondrial copies and found to be significantly higher in colorectal cancer patients than healthy controls (88 (58-154), p = 0.001). In the regression analysis, increased mitochondrial copy number variation was associated with risk of colorectal cancer (odds ratio = 2.885, 95% confidence interval = 1.3-6.358). However, T16189C polymorphism was found to be significantly associated with the risk of rectal cancer (odds ratio = 5.213, p = 0.001) and non-significantly with colon cancer (odds ratio = 0.867, p = 0.791). Also, false-positive report probability analysis was done to validate the significant findings. Our results here indicate that mitochondrial copy number variation may be playing an important role in the development of colorectal cancer, and detection of mitochondrial copy number variation can be used as a biomarker for predicting the risk of colorectal cancer in North Indian subjects.
在全球范围内，结直肠癌是第三大常见癌症类型。导致癌症发生的基因不稳定是癌症发展的主要原因之一。已知线粒体基因组的改变，即突变、单核苷酸多态性和拷贝数变异，在癌症发展中起作用。我们研究的目的是调查北印度人群中线粒体T16189C多态性和拷贝数变异与结直肠癌的关联。对126例结直肠癌患者和114名健康的北印度受试者外周血分离的DNA进行T16189C多态性分析，其中一半进行线粒体拷贝数变异分析。使用聚合酶链反应-限制性片段长度多态性进行基因分型，使用实时聚合酶链反应估计拷贝数变异，发现结直肠癌患者的线粒体拷贝数明显高于健康对照（88（58 - 154），p = 0.001）。在回归分析中，线粒体拷贝数变异增加与结直肠癌风险相关（比值比 = 2.885，95%置信区间 = 1.3 - 6.358）。然而，发现T16189C多态性与直肠癌风险显著相关（比值比 = 5.213，p = 0.001），与结肠癌无显著相关性（比值比 = 0.867，p = 0.791）。此外，进行了假阳性报告概率分析以验证显著结果。我们的结果表明，线粒体拷贝数变异可能在结直肠癌的发展中起重要作用，检测线粒体拷贝数变异可作为预测北印度受试者结直肠癌风险的生物标志物。
