Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer.
Clinical impact of MMP and TIMP gene polymorphisms in gastric cancer.
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MMP和TIMP基因多态性对胃癌的临床影响。
DOI：
10.1038/sj.bjc.6603307
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发表时间：
2006-09-18
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
胃癌表达增强水平的基质金属蛋白酶（MMPs）及其组织抑制剂（TIMPs）。MMP和TIMP基因的单核苷酸多态性（SNPs）可能与疾病易感性相关，也可能影响其抗原表达。我们研究了胃癌患者MMP-2、-7、-8和-9和TIMP-1和-2的SNP的基因型分布和等位基因频率与肿瘤进展、患者生存率和组织抗原表达的关系。除了MMP-7− 181 A>G外，胃癌患者和对照组的基因型分布和等位基因频率相似。此外，MMP-7− 181 A>G的基因型分布与幽门螺杆菌状态（χ2 7.8，P=0.005）和患者的肿瘤相关生存率相关。TIMP-2303 C>T多态性与WHO分型显著相关（χ 25.9，P=0.03），与肿瘤相关生存率显著相关（log rank 11.74，P=0.0006）。MMP-2、MMP-8、MMP-9和TIMP-1的单核苷酸多态性与肿瘤相关生存率无关。只有基因启动子MMP-2− 1306 C>T多态性与肿瘤内的蛋白水平显著相关。一级树状图聚类分析结合考克斯分析确定MMP-7− 181 A>G和TIMP-2303 C>T多态性组合对患者生存结局有重大影响。我们得出结论，MMP相关的SNP，特别是MMP-7− 181 A>G和TIMP-2303 C>T，可能有助于识别临床预后不良的胃癌患者。
Gastric cancers express enhanced levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Single-nucleotide polymorphisms (SNPs) in MMP and TIMP genes may be associated with disease susceptibility and might also affect their antigen expression. We studied the genotype distribution and allele frequencies of SNPs of MMP-2, -7, -8 and -9 and TIMP-1 and -2 in gastric cancer patients in relation to tumour progression, patient survival and tissue antigen expression. The genotype distribution and allele frequencies were similar in gastric cancer patients and controls, except for MMP-7−181A>G. In addition, the genotype distribution of MMP-7−181A>G was associated with Helicobacter pylori status (χ2 7.8, P=0.005) and tumour-related survival of the patients. Single-nucleotide polymorphism TIMP-2303C>T correlated significantly with the WHO classification (χ2 5.9, P=0.03) and also strongly with tumour-related survival (log rank 11.74, P=0.0006). Single-nucleotide polymorphisms of MMP-2, -8, -9 and TIMP-1 were not associated with tumour-related survival. Only the gene promoter MMP-2−1306C>T polymorphism correlated significantly with the protein level within the tumours. First-order dendrogram cluster analysis combined with Cox analysis identified the MMP-7−181A>G and TIMP-2303C>T polymorphism combination to have a major impact on patients survival outcome. We conclude that MMP-related SNPs, especially MMP-7−181A>G and TIMP-2303C>T, may be helpful in identifying gastric cancer patients with a poor clinical outcome.
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影响因子：
8.8
作者：
Duffy, M J;Blaser, J;Duggan, C;McDermott, E;O'Higgins, N;Fennelly, J J;Tschesche, H
通讯作者：
Tschesche, H
影响因子：
3.1
作者：
Joo, YE;Seo, KS;Kim, SJ
通讯作者：
Kim, SJ
影响因子：
24.3
作者：
Hirano, K;Sakamoto, T;Sekizawa, K
通讯作者：
Sekizawa, K
影响因子：
3.3
作者：
Lin, SC;Lo, SS;Chang, KW
通讯作者：
Chang, KW
影响因子：
8.8
作者：
通讯作者：
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