MiR-17-92基因簇启动子区SNPs及拷贝数变异与结直肠癌发病的关联研究

结直肠癌发病率高居我国恶性肿瘤的第三位，近年来，呈明显上升趋势，然而，其病因尚未完全阐明。多项证据证实，结直肠癌的发生与遗传因素有关。以往大量遗传关联性研究调查了编码基因中的单核苷酸多态性（SNPs）和拷贝数变异（CNV）与肿瘤的易感性，却很少涉及非编码基因如miRNA基因，尤其是发生在miRNA启动子区的遗传变异。研究表明，结直肠癌中miR-17-92基因簇显著高表达，多个癌基因或抑癌基因可通过与miR-17-92基因簇启动子区结合，调控细胞周期、增殖和凋亡等生物学过程，参与肿瘤的形成。由此推测，miR-17-92基因簇启动子区遗传变异可能与结直肠癌的发生有关。本研究拟联合使用SNPs和CNV两个遗传学标记，运用病例对照及功能实验探索miR-17-92基因簇启动子区遗传变异与结直肠癌发病的关联，旨在为阐明miR-17-92基因簇启动子区SNPs和CNV在结直肠癌发生发展中的作用提供依据。

Colorectal cancer (CRC) is the third most common malignant neoplasm in China, with an increasing incidence in recent years. The etiology, however, is still not fully known. Growing evidence has identified that genetic factors contribute to the development of CRC. Previously, a large number of studies have been performed to investigate the association between single nucleotide polymorphisms (SNPs) and copy number variation (CNV) in encoding genes and susceptibility to CRC. Nevertheless, only a few studies focused on the genetic variants in non-coding genes such as miRNA gene, especially in the promoter region of miRNA gene. It is evident that the level of miR-17-92 cluster was over-expressed in CRC tissues. Several oncogenes or tumor suppressor genes regulate cell cycle, proliferation, and apoptosis by binding to the promoter region of miR-17-92 cluster. Based on this background, we hypothesized that genetic variants in the promoter region of miR-17-92 cluster may be related to the development of CRC. In this study, we plan to examine the relationship between SNPs and CNV in the promoter region of miR-17-92 cluster and risk of CRC by conducting case-control and experimental studies. Additionally, the association between the SNPs and CNV and the high expression of miR-17-92 cluster in CRC will also be detected. We aim to provide evidence to clarify the role of the SNPs and CNV in the promoter region of miR-17-92 cluster playing in the development of CRC.