The Genotypes of IL-1 beta and MMP-3 are Associated with the Prognosis of HCV-related Hepatocellular Carcinoma
The Genotypes of IL-1 beta and MMP-3 are Associated with the Prognosis of HCV-related Hepatocellular Carcinoma
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DOI：
10.2169/internalmedicine.49.3268
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发表时间：
2010-01-01
影响因子：
1.2
通讯作者：
Yuasa, Isao
中科院分区：
文献类型：
--
作者：
Okamoto, Kinya;Ishida, Chihiro;Yuasa, Isao
背景与目的细胞因子和基质金属蛋白酶(MMPs)参与多种肿瘤的生长、侵袭和远处转移。最近，这些细胞因子和MMPs的功能基因多态性被发现，一些报道揭示了这些基因多态性与多种癌症的预后之间的关系。本研究探讨白细胞介素1β(IL-1b)、白介素1受体拮抗剂(IL-1RN)、转化生长因子β1(TGF-b1)、基质金属蛋白酶-1(MMP1)、基质金属蛋白酶-3(MMP3)和基质金属蛋白酶-9(MMP9)基因多态性与丙型肝炎病毒相关性肝细胞癌(HCC)预后的关系。方法对92例丙型肝炎相关肝细胞癌患者IL-1b-31C/T、IL-1RN可变数目串联重复序列(VNTR)、转化生长因子-β1+869C/T、基质金属蛋白酶-1-1、607G/2G、MMP1-1607G/2G、结果在肝细胞癌的临床特征中，转化生长因子b1C携带者和基质金属蛋白酶3 5A携带者的肝细胞癌直径明显大于转化生长因子b1T和基质金属蛋白酶3 6A纯合子。在肝细胞癌预后方面，IL-1b T纯合子和MMP3 5A携带者的预后明显差于IL 1bC携带者和MMP3 6A纯合子。结论IL-1b-31T等位基因和基质金属蛋白酶-3 5A等位基因是肝细胞癌患者预后不良的协同危险因素，提示这些基因多态性可能是预测肝细胞癌患者预后的潜在指标。
Background and Aim Cytokines and matrix metalloproteinases (MMPs) are involved in tumor growth, invasion, and remote metastasis in various cancers. Recently, functional gene polymorphisms in these cytokines and MMPs have been found, and some reports have revealed an association between these polymorphisms and the prognosis of various cancers. In this study, we examined the relationship between the gene polymorphisms of interleukin 1 beta (IL-1b), IL-1 receptor antagonist (IL-1 RN), transforming growth factor beta 1 (TGF-b1), MMP-1, MMP-3, and MMP-9 and the prognosis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).Methods We enrolled 92 HCV-related HCC patients in the study, and gene polymorphisms of IL-1b -31 C/T, IL-1 RN variable number of tandem repeats (VNTR), TGF-b1 +869 C/T, MMP-1 -1,607 1G/2G, MMP-3 1,171 5A/6A, and MMP-9 -1,562 C/T were analyzed.Results In HCC clinical features, TGF-b1 C carriers and MMP-3 5A carriers had significantly larger HCC diameters than TGF-b1 T and MMP-3 6A homozygotes. In HCC prognosis, IL-1b T homozygotes and MMP-3 5A carriers had a significantly poorer prognosis than IL-1b C carriers and MMP-3 6A homozygotes. Those with a combination of IL-1b T homozygosity and MMP-3 5A had synergistically poorer HCC prognosis.Conclusion The IL-1b -31 T allele and MMP-3 5A allele are cooperative risk factors for poor prognosis in HCC patients, suggesting that these gene polymorphisms might be potential markers for predicting the prognosis of HCC patients.