Wang Yimin, Fang Shumei, Wei Lizhen, Wang Rui, Jin Xia, Wen Denggui, Li Yan, Guo Wei, Wang Na, Zhang Jianhui
Hebei Cancer Institute, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, Hebei Province, China.
Lung Cancer. 2005 Aug;49(2):155-61. doi: 10.1016/j.lungcan.2005.04.006.
The matrix metalloproteinases (MMPs) are a family of highly conserved metal-dependent proteolytic enzymes, their main function is to degrade different components of extracellular matrix (ECM). Moreover, they play roles in regulation of cell growth, apoptosis, angiogenesis and immune surveillance. Natural sequence variations in the MMP genes may result in differential expression of MMPs in different individuals and therefore may be associated with the development and progression of diseases. The aim of this study is to assess the effects of the C-1562T polymorphism in the MMP-9 promoter on the risk of occurrence and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). The MMP-9 genotyping was performed in 243 pathologically diagnosed NSCLC patients and 350 healthy controls without overt cancer by using polymerase chain reaction-restriction fragment length polymorphism analysis. The distribution of the MMP-9 genotypes in NSCLC patients and healthy controls was in consistent with Hardy-Weinberg equilibrium. The frequency of the C/C, C/T and T/T genotypes in healthy controls was 79.4, 20.6 and 0%, respectively. Neither the overall genotype nor allelotype distribution in NSCLC patients showed significant difference from that in healthy controls (P=0.21 and 0.43, respectively). Compared with the C/C genotype, genotypes with the T allele did not show significant influence on the risk of NSCLC development (age and gender adjusted OR=1.13, 95% CI=0.76-1.68). Stratification by onset age, smoking status and tumor histological type also showed no association between the MMP-9 polymorphism and the risk of NSCLC. Furthermore, the genotype distribution between NSCLC patients with and without lymphatic metastasis was not significantly different. Therefore, the present study suggests that the MMP-9 C-1562T polymorphism may not be used as a useful marker to predicate susceptibility and lymphatic metastasis in NSCLC.
基质金属蛋白酶(MMPs)是一类高度保守的金属依赖性蛋白水解酶,其主要功能是降解细胞外基质(ECM)的不同成分。此外,它们在细胞生长、凋亡、血管生成和免疫监视的调节中发挥作用。MMP基因的天然序列变异可能导致MMPs在不同个体中的差异表达,因此可能与疾病的发生和发展有关。本研究的目的是评估MMP-9启动子中C-1562T多态性对非小细胞肺癌(NSCLC)发生风险和淋巴转移的影响。通过聚合酶链反应-限制性片段长度多态性分析,对243例经病理诊断的NSCLC患者和350例无明显癌症的健康对照进行了MMP-9基因分型。NSCLC患者和健康对照中MMP-9基因型的分布符合Hardy-Weinberg平衡。健康对照中C/C、C/T和T/T基因型的频率分别为79.4%、20.6%和0%。NSCLC患者的总体基因型和等位基因型分布与健康对照均无显著差异(P分别为0.21和0.43)。与C/C基因型相比,携带T等位基因的基因型对NSCLC发生风险无显著影响(年龄和性别校正后的OR=1.13,95%CI=0.76-1.68)。按发病年龄、吸烟状况和肿瘤组织学类型分层分析也显示MMP-9多态性与NSCLC风险之间无关联。此外,有和无淋巴转移的NSCLC患者之间的基因型分布无显著差异。因此,本研究表明MMP-9 C-1562T多态性可能不能作为预测NSCLC易感性和淋巴转移的有用标志物。