Matsumura Shunji, Oue Naohide, Nakayama Hirofumi, Kitadai Yasuhiko, Yoshida Kazuhiro, Yamaguchi Yoshiyuki, Imai Kazue, Nakachi Kei, Matsusaki Keisuke, Chayama Kazuaki, Yasui Wataru
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan.
J Cancer Res Clin Oncol. 2005 Jan;131(1):19-25. doi: 10.1007/s00432-004-0621-4. Epub 2004 Sep 30.
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.
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.
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).
Our results indicate that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer.
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起关键作用。据报道，MMP-9启动子-1562位的胞嘧啶（C）-胸腺嘧啶（T）单核苷酸多态性（SNP）会影响该基因的表达。本研究旨在探讨-1562 C/T多态性与胃癌发生发展的关系。
研究人群包括177例胃癌患者和224例健康对照者。采用聚合酶链反应-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。比较患者和对照者的基因型频率，并研究基因型与临床病理特征的相关性。
胃癌患者的基因型频率与对照者相似（P = 0.223）。然而，在胃癌患者中发现肿瘤侵袭程度、临床分期和淋巴侵袭与MMP-9多态性之间存在显著相关性（每项P<0.05）。
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。
