细胞增殖通路中miRNA及其作用靶点的基因多态性与结直肠癌遗传易感性的流行病学研究

It is estimated that miRNAs regulate more than 1/3 human genes. A large amount of studies have demonstrated that miRNAs have been implicated in the regulation of a variety of biological processes, including apoptosis, proliferation, cellular differentiation, gene regulation as well as the occurrence and development of cancers. According to the expression profile of miRNAs reported by articles, we found that miRNAs that regulating cell proliferation were frequently dysregulated in colorectal cancers. As a result, hypothesis was established that the genetic polymorphisms in miRNA or miRNA binding areas might influence the bonding between miRNAs and the target genes and the expression of the target genes would be influenced finally. To testify the hypothesis a case-control study was designed. Five-hundred colorectal cancer patients will be collected based on the surveillance system of cancer and hospitals in Hangzhou city. Meanwhile five-hundred frequency-matched controls will be involved from the same community with patients. The information will be collected by the questionnaire from study subjects including individual characteristics, lifestyles, diet, physical activities and family history of cancer. At the same time 2ml peripheral blood is drawn from subjects for DNA extraction. Bio-information and biosoftware are used to identify genetic polymorphisms within the miRNAs or their bonding areas, which will be detected by specific probes or restrictive enzymes. By applying multiple statistical methods such as Logistic regression, Multifactor Dimensionality Reduction, Classification and Regression Tree, the association mechanisms between genetic polymorphisms in miRNA or related target sites and colorectal cancer risk will be verified based on the population level. Moreover, the multivariate interactions among miRNA genes and environmental factors will be explored. Our study will enrich the genetic information of miRNA of Chinese population. And it also will contribute to strategies for the three-level prevention of colorectal cancer.

研究表明miRNAs调控着超过1/3的人类基因，在机体发育、细胞分化、增殖、凋亡等方面均发挥着重要作用，并参与着人类癌症发生发展。基于结直肠癌miRNA表达谱研究，发现细胞增殖通路上的miRNA表达异常与结直肠癌关系最为密切。本次研究即围绕增殖调控通路的miRNA及miRNA结合靶点与结直肠癌遗传易感性的关联进行探讨，拟在人群层面从基因多态性角度检验功能性miRNA与结直肠癌发病与预后关联。研究将选取我国结直肠癌高发区东南沿海地区为研究现场，依托肿瘤监测、医院、社区为平台，收集500例结直肠癌病例和500例人群对照作为研究对象，应用人类基因组学和生物功能学识别增殖调控通路上miRNA及靶点的基因多态位点，通过病例对照设计探索miRNA单基因、基因-基因、基因-环境多因素联合效应与结直肠癌发病风险及预后关联。研究发现将为拓展我国人群miRNA遗传学信息，开展结直肠癌的人群三级预防提供理论依据