Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas
Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas
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DOI：
10.1111/j.1600-0714.2004.00214.x
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发表时间：
2004-07-01
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;Chung, MY;Chang, KW
背景：口腔鳞状细胞癌(OSCC)和口腔粘膜下纤维化(OSF)与槟榔的使用高度相关，在大多数亚洲国家都很常见。基质金属蛋白酶(MMPs)是金属依赖蛋白水解酶的超家族，参与细胞外基质的降解。人基质金属蛋白酶-1(MMP1)基因启动子区域存在插入/缺失(-1607 2G->；1G)多态性，导致转录活性改变。这种基因型别与癌症发生和转移的风险有关。方法：对121例口腔鳞癌患者、58例口腔鳞癌患者和147例正常对照的血液DNA进行聚合酶链式反应(PCR)基因分型。口腔鳞癌按受累部位分为颊鳞状细胞癌(BSCC)和非颊鳞状细胞癌(NBSCC)。结果：口腔鳞状细胞癌(OSCC)组(0.69，P=0.06)和NBSCC组(0.76，P=0.03)中，MMP1启动子的2G基因型频率明显高于对照组(0.63)，OR值分别为2.17和4.58。该基因与OSF的发病风险无关。结论：MMP1基因启动子的2G基因型与口腔鳞癌的发病风险相关。
BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF), which are highly associated with areca use, are prevalent in most Asian countries. Matrix metalloproteinases (MMPs) are superfamily of metal-dependent proteolytic enzymes, mediating the degradation of extracellular matrix. Insertion/deletion (-1607 2G-->1G) polymorphism has been described in the promoter region of the human matrix metalloproteinases-1 (MMP-1) genes, which cause an alteration in the transcriptional activity. This genotype is associated with risks of cancer genesis and metastasis. In this paper, we studied the relationship between such genotype and areca-associated oral diseases.METHODS: Genomic DNA from the blood of OSCC (n = 121), OSF (n = 58) cases and controls (n = 147) were amplified by polymerase chain reaction (PCR)-based genotyping. The OSCC were further grouped into buccal squamous cell carcinoma (BSCC) and non-buccal suqmaous cell carcinoma (NBSCC), in accord with the site of involvement. The significance of the differences was assessed by Fisher's exact test.RESULTS: The 2G genotype in MMP-1 promoter was observed with a higher frequency in both OSCC (0.69, P = 0.06) and NBSCC (0.76, P = 0.03) cases compared with controls (0.63), with an odds ratio of 2.17 and 4.58, respectively. This genotype was not related to the risk of OSF. No other clinicopathologic parameter was associated with the genotypes in OSCC cases.CONCLUSION: The results showed that 2G genotype in MMP-1 promoter was associated with the risk of OSCC.