The association of MMP-1, -3 and -9 genotypes with the prognosis of HCV-related hepatocellular carcinoma patients.

Kinya Okamoto, Mari Mandai, Kenichi Mimura, Yoshikazu Murawaki, Isao Yuasa
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Abstract

Background/aims: Matrix metalloproteinases (MMPs) play important roles in cancer invasion and metastasis. Recently, functional gene polymorphisms in the promoter regions of MMP-1 1G/2G, MMP-3 5A/6A and MMP-9 C/T have been found, and have been reported to be associated with the prognosis of various cancers. In this study, we examined the association of the MMP-1, -3, -9 genotypes with the prognosis of hepatocellular carcinoma (HCC).

Methods: Ninety two patients with hepatitis C virus related HCC were enrolled in the study. Genomic DNA samples were extracted from peripheral white blood cells, and gene polymorphisms of MMP-1, MMP-3and MMP-9 were analyzed by PCR-RFLP methods.

Results: There were no significant differences of the survival rate between MMP-1 1G carriers and 2G homozygotes, and between MMP-9 T carriers and C homozygotes. By contrast, HCC patients with MMP-35A allele had a significantly poorer prognosis than 6A homozygotes.

Conclusions: Unlike MMP-1 and MMP-9 genotypes, MMP-3 5A allele, with higher transcriptional activity, may be a risk factor for the poor prognosis of HCC patients.

MMP-1、-3和-9基因型与丙型肝炎相关肝癌患者预后的关系
背景/目的:基质金属蛋白酶(Matrix metalloproteinases, MMPs)在肿瘤侵袭转移过程中起重要作用。近年来,MMP-1 1G/2G、MMP-3 5A/6A和MMP-9 C/T启动子区域的功能基因多态性被发现,并被报道与多种癌症的预后相关。在这项研究中,我们检测了MMP-1、-3、-9基因型与肝细胞癌(HCC)预后的关系。方法:对92例丙型肝炎病毒相关HCC患者进行研究。提取外周血细胞基因组DNA样本,采用PCR-RFLP方法分析MMP-1、mmp -3和MMP-9基因多态性。结果:MMP-1 1G携带者与2G纯合子、MMP-9 T携带者与C纯合子生存率无显著差异。相比之下,携带MMP-35A等位基因的HCC患者预后明显差于携带6A纯合子的HCC患者。结论:与MMP-1和MMP-9基因型不同,MMP-3 5A等位基因具有较高的转录活性,可能是HCC患者预后不良的危险因素。
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