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细胞周期蛋白D1 G870A多态性与中国人群肝细胞癌风险

Cyclin D1 G870A polymorphism and the risk of hepatocellular carcinoma in a Chinese population.

作者信息

Hu Zhangyong, Zhou Zhipeng, Xiong Guolian, Wang Yali, Lai Yi, Deng Lan, Yang Jinliang

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.

出版信息

Tumour Biol. 2014 Jun;35(6):5607-12. doi: 10.1007/s13277-014-1741-3. Epub 2014 Feb 26.

Abstract

Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the cell cycle transition from G1 phase to S phase. A common polymorphism (G870A) in the exon 4 of CCND1 gene affects splicing of the CCND1 transcript and may cause uncontrollable cellular growth. Therefore, the CCND1 G870A polymorphism may influence an individual's susceptibility to the development of certain tumors. The present study was performed to test the association between G870A polymorphism in the CCND1 gene and hepatocellular carcinoma (HCC) risk in a Chinese population. We extracted the peripheral blood samples from 220 patients with HCC and 220 age- and gender-matched healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and direct DNA sequencing were performed to detect the polymorphism. The CCND1 genotype distribution among HCC patients was not significantly different from that among healthy controls (P=0.08). Compared with the wild-type GG genotype, neither the variant AA genotype nor the variant genotypes containing the A allele were associated with risk of HCC. However, stratification analysis by HBV carrier status revealed that the variant genotypes containing the A allele were associated with a significantly increased risk of HCC among HBsAg-positive individuals (adjusted OR=3.87; 95 % CI=1.12, 13.30). These results suggest that the CCND1 G870A polymorphism may increase the risk of HBV-related HCC in the Chinese population.

摘要

细胞周期蛋白D1由CCND1基因编码,是细胞从G1期过渡到S期的一种调节蛋白。CCND1基因第4外显子的常见多态性(G870A)影响CCND1转录本的剪接,并可能导致细胞生长失控。因此,CCND1 G870A多态性可能影响个体对某些肿瘤发生的易感性。本研究旨在检测中国人群中CCND1基因G870A多态性与肝细胞癌(HCC)风险之间的关联。我们从220例HCC患者和220例年龄及性别匹配的健康对照中采集外周血样本。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析和直接DNA测序检测多态性。HCC患者中CCND1基因型分布与健康对照者无显著差异(P = 0.08)。与野生型GG基因型相比,变异型AA基因型和含有A等位基因的变异基因型均与HCC风险无关。然而,按乙肝病毒携带者状态进行分层分析显示,在HBsAg阳性个体中,含有A等位基因的变异基因型与HCC风险显著增加相关(校正OR = 3.87;95%CI = 1.12,13.30)。这些结果表明,CCND1 G870A多态性可能增加中国人群中乙肝病毒相关HCC的风险。

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