MMP-1基因1G/2G多态性在胃癌侵袭转移中的作用

The role of 1G/2G polymorphism in MMP-1 gene on invasiveness of gastric cancer

背景与目的:基质金属蛋白酶-1(Matrixmetalloproteinase-1,MMP-1)通过降解细胞外基质和基底膜屏障促进肿瘤的浸润转移,本研究探讨MMP-1基因1G/2G多态性在胃癌人群中的分布及其与胃癌侵袭转移的关系。方法:采用聚合酶链反应PCR-变性高效液相色谱分析(denaturinghighperformanceliquidchromatography,DHPLC)方法,对102例胃癌患者进行MMP-1基因1G/2G多态性的基因型分析,比较基因型分布和胃癌组织浸润转移等侵袭性指标的关系。结果:MMP-1基因1G/2G多态的1G/1G、1G/2G和2G/2G基因型在胃癌患者中的分布频率分别为15(14.7%)、48(47.1%)、39(38.2%);1G/2G多态性基因型分布与胃癌淋巴结转移程度(N1vsN2+N3)显著相关(P=0.013);与1G/1G纯合子基因型相比,携带2G等位基因型的胃癌患者淋巴结转移更严重(P<0.05)。1G/2G基因型分布与胃癌组织学类型,肿瘤部位,组织病理分级及胃壁浸润深度(T1+T2vsT3+T4),临床病期等无明显相关(P>0.05)。结论:MMP-1基因1G/2G多态性与胃癌的侵袭性有关,携带2G等位基因可能是胃癌淋巴结转移的危险因素。

Background and purpose： Matrix metalloproteinase-1 （MMP-1） has been reported to be involved in cancer invasion and metastasis by degradation of extracellular matrix （ECM） and basement membrane barriers. The present study is to investigate the association between 1G/2G polymorphism in MMP-1 gene and invasiveness of gastric cancer. Methods： 102 gastric cancer patients were included in the study. Genotype analysis was performed by using polymerase chain reaction （PCR） -based denaturing high performance liquid chromatography （ DHPLC）, The relationship between this SNP（single nucleotide polymorphism） and cancer invasiveness was evaluated by comparing clinicopathologic parameters of the patients with gastric cancer. Results： The distributions for 1G/1G, 1G/2G and 2G/2G genotype of MMP-1 1G/2G polymorphism were 15（14.7%）, 48（47.1% ）, 39（38.2%）, respectively. A strong correlation was found between the genotype distribution and lymph node metastasis of gastric cancer（ P = 0. 013）. the patients with 2G/2G or 1G/2G genotype carriers had more lymph node metastasis than the one with 1G homozygous genotype carriers （P 〈 0.05）. 1G/2G polymorphism was not found any significant difference among the groups with variable genotype frequency and tumor histology type, lesion location, tumor invasion depth （T1 ＋ T2 vs T3 ＋ T4） and clinical staging of gastric cancer. Conclusions： 1G/2G polymorphism in MMP-1 gene promoter may play a role in aggressiveness of gastrie cancer and 2G allele could be associated with increased lymph node metastasis of gastric cancer.