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背景与目的:基质金属蛋白酶(matrix metalloproteinases,MMPs)是肿瘤发生、侵袭和转移过程中的关键酶之一。MMPs基因启动子区的单核苷酸多态性(single nucleotide polymorphism,SNPs)可通过影响基因的转录和蛋白的表达而影响肿瘤的发生、发展。本研究旨在探索MMP-3、MMP-7启动子区基因多态性与脑星形胶质细胞瘤发病风险的关系。方法:以聚合酶链反应-限制性片段长度多态性分析方法,检测236例成人星形胶质细胞瘤及365例健康对照的MMP-3-11715A/6A及MMP-7-181A/G多态性的基因型。结果:(1)MMP-3等位基因型及基因型总体分布在肿瘤患者组和健康对照组之间差异无统计学意义(P>0.05)。根据性别、发病年龄、病理分级进行的分层分析显示,与6A/6A基因型相比,MMP-35A/5A和5A/6A基因型个体患肿瘤的发病风险与其它基因型个体差异无统计学意义;(2)MMP-7基因型在肿瘤患者组及健康对照组中的分布差异有统计学意义(P=0.001)。与A/A基因型相比,A/G及G/G基因型可显著增加星形胶质细胞瘤的发病风险,经性别、年龄较正的OR值分别为1.69及2.77(95%CI=1.01～2.84及1.27～6.02)。分层分析显示,G/G基因型可使45岁以下人群及男性个体发生星形胶质细胞瘤的风险增加3倍左右,G/G基因型携带者发生Ⅱ～Ⅳ级星形胶质细胞瘤的风险增加3倍左右,且A/G基因型可增加Ⅱ级星形胶质细胞瘤的发病风险约2倍。结论:MMP-7-181A/G多态性可能影响星形胶质细胞瘤的发病风险,而MMP-3-11715A/6A多态性与此肿瘤的易感性可能无关。
BACKGROUND & AIM: Matrix metalloproteinases (MMPs) are one of the key enzymes in tumorigenesis, invasion and metastasis. Single nucleotide polymorphisms (SNPs) in the promoter regions of MMPs gene influence the development and progression of tumors by affecting gene transcription and protein expression. The purpose of this study was to explore the relationship between the gene polymorphisms of MMP-3 and MMP-7 promoter regions and the risk of astrocytoma. Methods: The polymorphisms of MMP-3-11715A / 6A and MMP-7-181A / G in 236 adult astrocytomas and 365 healthy controls were detected by polymerase chain reaction-restriction fragment length polymorphism Genotype. Results: (1) There was no significant difference in the overall distribution of MMP-3 allele and genotype between cancer patients and healthy controls (P> 0.05). Hierarchical analysis based on sex, age of onset, and pathological grade showed that there was no statistical difference in the incidence of cancer between individuals with MMP-35A / 5A and 5A / 6A genotypes and those with other genotypes as compared with 6A / 6A genotypes Significance; (2) The distribution of MMP-7 genotypes in cancer patients and healthy controls was significantly different (P = 0.001). Compared with A / A genotype, A / G and G / G genotypes could significantly increase the risk of astrocytoma. The odds ratios for gender and age were 1.69 and 2.77 (95% CI = 1.01 ~ 2.84 and 1.27 ~ 6.02). Hierarchical analysis showed that G / G genotypes increased the risk of astrocytoma by about 3 times in individuals under 45 years of age and in men, while those in G / G genotypes developed grade II-IV astrocytes The risk of neoplasia increased about 3 times, and A / G genotype increased the risk of grade Ⅱ astrocytoma about 2 times. Conclusion: MMP-7-181A / G polymorphism may affect the risk of astrocytoma. However, MMP-3-11715A / 6A polymorphism may not be related to the susceptibility of this tumor.