pri-miR-34启动子基因多态性与肝细胞癌风险的相关性研究

发布时间：2019-06-07 07:09

【摘要】：目的:肝细胞癌是全球范围内常见的恶性肿瘤之一,占全球恶性肿瘤发病率的第5位,死亡率的第3位,是我国恶性肿瘤第二大死因。该疾病常由环境因素和基因因素导致。miRNA表达失调与肿瘤的发生发展密切相关,其作用具有广泛性和复杂性,miRNA可以通过调节致癌基因和抑癌基因的表达导致肿瘤发生。MicroRNA-34(miR-34)功能繁多,能够参与细胞的增殖、分化以及凋亡等生理过程,并由此在细胞恶变过程中扮演非常重要的角色。因此,本研究探讨了pri-miR-34b/c启动子区域rs4938723的基因多态性与肝细胞癌风险的相关性。方法:随机纳入肝细胞癌患者286例,选取同期在我们医院门诊和健康体检中心参加健康体检的622人作为对照组。通过聚合酶链式反应-限制性片段长度多态(PCR-RFLP)分析技术评估患者pri-miR-34b/crs4938723的基因多态性。利用logistic回归分析,评估pri-miR-34b/c rs4938723基因多态性与肝细胞癌风险的相关性。结果:与对照组相比,肝细胞癌患者的年龄(χ2= 13.21,P0.001)、男性比例(χ2=0.09,P =0.76)和吸烟(χ2 = 0.53,P = 0.46)无明显相关性。相对于 pri-miR-34b/c启动子rs4938723的TT基因型,TC基因型(校正后OR = 2.97,95%CI = 1.80-4.37)和CC基因型(校正后OR = 1.72,95%CI = 1.05-5.20)都有更高的患肝细胞癌风险。而且,相对TT基因型,TC+CC基因型进一步增加了患肝细胞癌的风险(校正后 OR = 1.90,95%CI= 1.41-2.54)。在隐性模型中,与 pri-miR-34b/crs4938723的TT+TC基因型相比,CC基因型与肝细胞癌高风险显著相关(校正后OR = 2.26,95%CI =1.40-3.65)。而较pri-miR-34b/crs4938723 携带的 T等位基因,pri-miR-34b/c rs4938723携带的C等位基因型与肝细胞癌风险升高显著正相关(对性别、年龄、吸烟进行校正,校正后 OR= 1.70,95%CI = 1.38-2.10,P0.001)。结论:pri-miR-34b/crs4938723的基因多态性与肝细胞癌风险具有明显的相关性。
[Abstract]:Objective: hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, accounting for the fifth and third highest incidence and mortality of malignant tumors in the world. it is the second leading cause of death of malignant tumors in China. The disease is often caused by environmental and genetic factors. The imbalance of miRNA expression is closely related to the occurrence and development of tumor, and its effect is extensive and complex. MiRNA can lead to tumorigenesis by regulating the expression of carcinogenic genes and tumor suppressors. MicroRNA-34 (miR-34) has a wide range of functions and can participate in the physiological processes of cell proliferation, differentiation and apoptosis. Thus, it plays a very important role in the process of cell malignant transformation. Therefore, this study investigated the relationship between rs4938723 gene polymorphism in pri-miR-34b/c promoter region and the risk of hepatocellular carcinoma (HCC). Methods: 286 patients with hepatocellular carcinoma (HCC) were randomly included. 622 patients who took part in physical examination in outpatient department and health examination center of our hospital at the same time were selected as control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to evaluate the gene polymorphism of pri-miR-34b/crs4938723 in patients. Logistic regression analysis was used to evaluate the relationship between pri-miR-34b/c rs4938723 gene polymorphism and the risk of hepatocellular carcinoma (HCC). Results: compared with the control group, there was no significant correlation between the age of patients with hepatocellular carcinoma (蠂 2 = 13.21, P0.001), the proportion of males (蠂 2 鈮，

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