A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer

A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer
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DOI:
10.1007/s00432-004-0621-4
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发表时间:
2005-01-01
影响因子:
3.6
通讯作者:
Yasui, W
Yasui, W
中科院分区:
医学3区
文献类型:
--
作者:
Matsumura, S;Oue, N;Yasui, W

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目的:基质金属蛋白酶-9(MMP-9,明胶酶 B)通过降解细胞外基质(ECM)和基底膜屏障,在癌症侵袭和转移中发挥关键作用。据报道,MMP-9 启动子中 -1562 位的胞嘧啶 (C)-胸苷 (T) 单核苷酸多态性 (SNP) 会影响该基因的表达。本研究的目的是探讨-1562 C/T多态性与胃癌发生、发展的关系。方法:研究人群包括 177 名胃癌患者和 224 名健康对照受试者。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和测序分析MMP-9启动子中的SNP。比较患者和对照之间的基因型频率,并研究基因型与临床病理特征的关联。结果:胃癌患者的基因型频率与对照组相似(P = 0.223)。然而,胃癌患者的肿瘤侵犯程度、临床分期、淋巴管侵犯与MMP-9多态性之间存在显着相关性(P < 0.05)。结论:我们的结果表明MMP-9启动子中的T等位基因与胃癌的侵袭表型相关。
Purpose: Matrix metalloproteinase-9 (MMP-9, gelatinase B) plays a key role in cancer invasion and metastasis by degradating the extracellular matrix (ECM) and basement membrane barriers. A cytosine (C)-thymidine ( T) single nucleotide polymorphism (SNP) at position -1562 in the MMP-9 promoter is reported to affect expression of this gene. The purpose of this study was to investigate the relation between the -1562 C/T polymorphism and the development and progression of gastric cancer. Methods: The study population included 177 gastric cancer patients and 224 healthy control subjects. The SNP in the MMP-9 promoter was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological features was studied. Results: Genotype frequencies in gastric cancer patients were similar to those in control subjects (P = 0.223). However, significant association was found between degree of tumor invasion, clinical stage, and lymphatic invasion and the MMP-9 polymorphism in gastric cancer patients (P < 0.05, for each). Conclusions: Our results indicate that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer.