【摘要】：目的:肝細(xì)胞癌是全球范圍內(nèi)常見的惡性腫瘤之一,占全球惡性腫瘤發(fā)病率的第5位,死亡率的第3位,是我國惡性腫瘤第二大死因。該疾病常由環(huán)境因素和基因因素導(dǎo)致。miRNA表達(dá)失調(diào)與腫瘤的發(fā)生發(fā)展密切相關(guān),其作用具有廣泛性和復(fù)雜性,miRNA可以通過調(diào)節(jié)致癌基因和抑癌基因的表達(dá)導(dǎo)致腫瘤發(fā)生。MicroRNA-34(miR-34)功能繁多,能夠參與細(xì)胞的增殖、分化以及凋亡等生理過程,并由此在細(xì)胞惡變過程中扮演非常重要的角色。因此,本研究探討了pri-miR-34b/c啟動子區(qū)域rs4938723的基因多態(tài)性與肝細(xì)胞癌風(fēng)險的相關(guān)性。方法:隨機(jī)納入肝細(xì)胞癌患者286例,選取同期在我們醫(yī)院門診和健康體檢中心參加健康體檢的622人作為對照組。通過聚合酶鏈?zhǔn)椒磻?yīng)-限制性片段長度多態(tài)(PCR-RFLP)分析技術(shù)評估患者pri-miR-34b/crs4938723的基因多態(tài)性。利用logistic回歸分析,評估pri-miR-34b/c rs4938723基因多態(tài)性與肝細(xì)胞癌風(fēng)險的相關(guān)性。結(jié)果:與對照組相比,肝細(xì)胞癌患者的年齡(χ2= 13.21,P0.001)、男性比例(χ2=0.09,P =0.76)和吸煙(χ2 = 0.53,P = 0.46)無明顯相關(guān)性。相對于 pri-miR-34b/c啟動子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)都有更高的患肝細(xì)胞癌風(fēng)險。而且,相對TT基因型,TC+CC基因型進(jìn)一步增加了患肝細(xì)胞癌的風(fēng)險(校正后 OR = 1.90,95%CI= 1.41-2.54)。在隱性模型中,與 pri-miR-34b/crs4938723的TT+TC基因型相比,CC基因型與肝細(xì)胞癌高風(fēng)險顯著相關(guān)(校正后OR = 2.26,95%CI =1.40-3.65)。而較pri-miR-34b/crs4938723 攜帶的 T等位基因,pri-miR-34b/c rs4938723攜帶的C等位基因型與肝細(xì)胞癌風(fēng)險升高顯著正相關(guān)(對性別、年齡、吸煙進(jìn)行校正,校正后 OR= 1.70,95%CI = 1.38-2.10,P0.001)。結(jié)論:pri-miR-34b/crs4938723的基因多態(tài)性與肝細(xì)胞癌風(fēng)險具有明顯的相關(guān)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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