Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for oral carcinogenesis
Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for oral carcinogenesis
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DOI：
10.1111/j.1600-0714.2004.00231.x
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发表时间：
2004-08-01
影响因子：
3.3
通讯作者：
Chang, KW
中科院分区：
文献类型：
--
作者：
Lin, SC;Lo, SS;Chang, KW
背景技术背景：基质金属蛋白酶-2（MMP-2）可降解细胞外基质和基底膜，在口腔鳞状细胞癌（OSCC）等多种肿瘤的发生、发展中起重要作用。MMP-2启动子-1306C->T多态性破坏了Sp1结合位点，导致转录活性降低。本研究旨在评估这种基因型与口腔鳞状细胞癌和口腔粘膜下纤维性变（OSF）风险的关系，OSF是一种癌前状态，表现出过度的胶原蛋白产生，并在病因学上与槟榔的使用有关。121例口腔鳞状细胞癌患者血液样本的基因组DNA，采用聚合酶链反应（PCR）扩增58例OSF患者和147例对照者的DNA，变性高效液相色谱（dHPLC）分析其基因型。根据累及部位，OSCC进一步分为颊鳞状细胞癌（BSCC）和非颊鳞状细胞癌（NBSCC）。结果：CC基因型与CT、TT基因型相比，患口腔鳞癌的危险性增加近2倍。携带CC基因型的受试者发生NBSCC的风险更明显（大于4倍）。然而，在携带这种基因型的口腔鳞癌病例中，没有发现淋巴结转移或晚期的风险增加。结论：MMP-2启动子功能基因型是口腔癌发生的危险因素，尤其是在非颊部发生的亚群中，CC基因型与BSCC或OSF的发生无显著相关性。
BACKGROUND: Matrix metalloproteinase-2 (MMP-2) can degrade extracellular matrix and basement membrane, and play an important role in the development and progression of multiple carcinomas, including oral squamous cell carcinoma (OSCC). A -1306C-->T polymorphism in the MMP-2 promoter disrupts Sp1-binding site, and results in reduction of transcriptional activity. This study aimed to assess the association of such genotype with the risk of OSCC and oral submucous fibrosis (OSF), which is a precancerous condition that exhibits excessive collagen production and etiologically links to areca use.METHODS: Genomic DNA from the blood samples of 121 OSCC cases, 58 OSF cases and 147 controls were amplified by polymerase chain reaction (PCR) and subjected to denaturing high-performance liquid chromatography (dHPLC) analysis for genotyping. The OSCC were further classified into buccal squamous cell carcinoma (BSCC) and non-buccal squamous cell carcinoma (NBSCC), according to the site of involvement. Fisher's exact test and unconditional logistic regression models were used for statistical analysis.RESULTS: Subjects carrying CC genotype had nearly twofold increased risk for developing OSCC when comparing with CT or TT genotype. Subjects carrying CC genotype had more apparent risk (greater than fourfold) for developing NBSCC. However, no increase in risk for lymph node metastasis or advanced stage was identified in OSCC cases carrying such genotype. Preliminarily data suggest no significant association between subjects carrying CC genotype and the development of BSCC or OSF.CONCLUSION: This is the first paper demonstrating that functional genotype of MMP-2 promoter is a risk factor for oral carcinogenesis, particularly for the subsets occurring on non-buccal site.