Relation between single nucleotide polymorphism (SNP) of gastric carcinogenesis- and cancer progression -associated genes and peritumoral stromal reaction in early gastric cancer

据报道，HER2基因（Ile/Val,A/G）跨膜结构域的单核苷酸多态性（SNP）与乳腺癌的风险相关。因此，研究HER-2多态性与胃癌的关系。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和测序技术对HER2基因SNP进行分析。212例胃癌患者中分别有146例（68.9%）、56例（26.4%）和10例（4.7%）存在Ile/Ile、Ile/Val和Val/Val基因型，287例对照中分别有234例（81.5%）、48例（16.7%）和5例（1.8%）存在Ile/Ile、Ile/Val基因型。在患者中，Ile/Val或Val/Val基因型患者的晚期癌发生率明显高于Ile/Ile基因型患者（p<0.001）。HER-2基因型与肿瘤侵袭、淋巴结转移和远处转移密切相关。HER-2基因多态性与早期胃癌肿瘤边界间质反应（界限清楚与否）无相关性。据报道，基质金属蛋白酶-9（MMP-9，明胶酶B）启动子-1562位的胞嘧啶(C)-胸腺嘧啶(T)单核苷酸多态性（SNP）影响该基因的表达。探讨-1562 C/T多态性与胃癌发生发展的关系。研究了基因型与临床病理特征的关系。胃癌患者肿瘤侵袭程度、临床分期、淋巴侵袭与MMP-9多态性有显著相关性（P均<0.05），说明MMP-9启动子中的T等位基因与胃癌侵袭表型相关。MMP-9基因启动子多态性与早期胃癌肿瘤边界间质反应无相关性。死亡受体4（DR4）基因多态性与早期胃癌肿瘤边界间质反应无相关性。

A single nucleotide polymorphism(SNP) of HER2 gene (Ile/Val,A/G) in the transmembrane domain was reported to be associated with a risk of breast cancer. So association between the HER-2 polymorphism and gastric carcinoma was examined. The SNP in HER2 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing. The Ile/Ile,Ile/Val and Val/Val genotypes were found in 146(68.9%), 56(26.4%) and 10(4.7%) of 212 gastric cancer patients and in 234(81.5%), 48(16.7%) and 5(1.8%) of 287 control subjects, respectively. In patients, carcinomas of advanced stage were significantly more frequent in patients with Ile/Val or Val/Val genotype than those with Ile/Ile genotype (p<0.001). Tumor invasion, lymph node metastasis and distant metastasis were closely associated with the HER-2 genotype. There was no correlation between the HER-2 gene polymorphism and stromal reaction (well-circumscribed or not) at the tumor border of early gastric cancer.A cytosine(C)-thymidine(T) single nucleotide polymorphism(SNP) at position -1562 in the Matrix metalloproteinase-9(MMP-9, gelatinase B) promoter is reported to affect expression of this gene. So relation between the -1562 C/T polymorphism and the development and progression of gastric cancer was examined. Association of genotypes with clinicopathological features was studied. Significant association was found between degree of tumor invasion, clinical stage, and lymphatic invasion and the MMP-9 polymorphism in gastric cancer patients (P<0.05, for each), indicating that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer. There was no correlation between the MMP-9 gene promoter polymorphism and stromal reaction at the tumor border of early gastric cancer.There was no correlation between the Death Receptor 4(DR4) gene polymorphism and stromal reaction at the tumor border of early gastric cancer.