谷胱甘肽S-转移酶P1基因多态性与胃癌发展的相关性研究

目的分析谷胱甘肽S-转移酶（glutathione-S-transferase GSTs）P1基因多态性与胃癌发展的相关性,探讨高风险GSTP1-Val等位基因在氧自由基致胃癌中的作用。方法以血液样本、胃癌细胞和相应正常胃黏膜细胞样本为实验材料,采用放射免疫分析法（RIA）测定血浆谷胱甘肽S-转移酶P（GSTP）的含量和活性改变;多聚酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测外周血DNA GSTP1的多态性。结果胃癌、肠上皮化生和不典型增生两种癌前病变组织中GSTP染色的阳性率分别为78.00%（39/50）、48.00%（24/50）和74.00%（37/50）,与正常胃黏膜比较差异有统计学意义（P〈0.05）;GSTP在胃癌时升高（27.5±24.5）μg/L],明显高于正常人组（7.1±2.3）μg/L],两组比较差异有高度统计学意义（P〈0.01）;GSTP在癌前病变组（16.8±12.3）μg/L]高于正常人组（P〈0.01）;GSTP含量与肿瘤的分化程度呈正相关（r=0.914,P〈0.01）;高分化及中分化管状腺癌的阳性率分别为72.73%（8/11）和100.00%（21/21）,高于低分化管状腺癌（58.33%）,分化程度与GSTP表达呈正相关（r=0.732,P〈0.01）。Val 105的酶代替具有Lle 105的酶对多环芳烃二醇环氧化作用的效力高7倍,说明携带Val等位基因的个体患胃癌危险性明显高于非携带Val等位基因个体。结论 GSTP是机体损伤解毒的酶,它与肿瘤的发生、发展有关,是肿瘤早期诊断有价值的标志酶;GSTP1基因多态性与胃癌发展相关。携带GSTP1 Val等位基因的个体胃癌发病风险增高。

Correlation of Glutathione S-transferase P1 gene polymorphism and gastric cancer development

Objective To analyze correlation between Glutathione S-transferase P1 gene polymorphism and gastric cancer development,and explore the role of high-risk GSTP1-Val allele in gastric cancer induced by oxygen radicals.Methods The blood samples,gastric cancer cells,corresponding normal gastric mucosa cell samples were selected as experimental materials,radioimmunoassay（RIA） was used to determine the content and activity change of plasma glu tathione S-transferase P（GSTP）;polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） was used to detect peripheral blood DNA GSTP1 polymorphism.Results GSTP staining positive rate in gastric cancer,precancerous lesions of intestinal metaplasia and dysplasia were 78.00%（39/50）,48.00%（24/50） and 74.00%（37/50）,compared with normal gastric mucosa,difference was statistically significant（P ＆lt; 0.05）;GSTP in gastric cancer （27.5± 24.5） μg/L] increased,significantly higher than normal group （7.1 ±2.3） μg/L],the difference was statistically significant（P ＆lt; 0.01）;GSTP in precancerous lesions group （16.8 ±12.3） μg/L）] was higher than the normal group（P ＆lt; 0.01）;GSTP content was positively correlated with tumor differentiation degree（r = 0.914,P ＆lt; 0.01）;positive rate of welldifferentiated and moderately differentiated tubular adenocarcinoma were 72.73%（8/11） and 100.00%（21/21）,all were higher than the poorly differentiated tubular adenocarcinoma（58.33%）,degree of differentiation was positively corre lated with GSTP expression（r = 0.732,P ＆lt; 0.01）;effectiveness of Val 105 enzyme in polycyclic aromatic hydrocarbons diol epoxidation was 7 times of enzyme with Lle 105,it show that risk of gastric cancer in individuals with Val allele was significantly higher than individuals with no Val allele.Conclusion GSTP is not only the injury detoxification enzyme,it is related to genesis and development of tumor,is marker enzyme of tumor early diagnosis;GSTP1 gene poly morphism is related to gastric cancer development.Risk of gastric cancer of individuals carrying GSTP1 Val allele is high.