EZH2基因单核苷酸多态性对中国汉族人群散发性胃癌易感性的影响

Effect of EZH2 polymorphisms on sporadic gastric cancer susceptibility in Chinese Han population

目的研究EZH2基因单核苷酸多态性与汉族人群散发性胃癌易感性关系以及胃癌临床病理特征与EZH2蛋白表达的关系。方法采用基因测序仪对安徽地区311例胃癌患者及425例正常对照组血样EZH2 rs734004、rs734005、rs2072407、rs6464926和rs12670401多态性测序,用组织芯片技术和免疫组化检测238例同一来源胃癌组织和30例正常胃黏膜EZH2蛋白表达。结果 EZH2 rs12670401基因型CC以及rs6464926基因型TT在胃癌患者中比例较高,可增加胃癌发生风险（P=0.007,aOR=1.786,95%CI=1.172~2.723;P=0.013,aOR=1.721,95%CI=1.123~2.638）。胃癌患者中EZH2杂合基因型rs2072407TC、rs734005TC、rs734004CG比例低于对照组,可降低胃癌发生风险。（P=0.034,aOR=0.712,95%CI=0.520~0.975;P=0.033,aOR=0.709,95%CI=0.518~0.972;P=0.035,aOR=0.711,95%CI=0.518~0.976）。连锁不平衡分析LD进一步证实上述观察。胃癌不同组织学类型间以及不同临床参数间EZH2免疫组化染色强度差异无显著性。结论 EZH2基因单核苷酸多态性与中国汉民族人群散发性胃癌易感性相关。

Purpose To explore the association of the single nucleotide polymorphisms（SNPs） of EZH2 with susceptibility of sporadic gastric cancer in Chinese Han population.Methods EZH2 SNPs：rs734004,rs734005,rs2072407,rs6464926 and rs12670401 in 311 patients with gastric cancers and 425 controls were genotyped by using gene sequencing instruments.Expression of EZH2 in 238 cases of the gastric cancers and 30 cases of normal gastric mucosa were detected by tissue microarray-based immunohistochemistry.Results The genotype of CC（rs12670401） and the genotype of TT（rs6464926） elevated the risk of gastric cancer（P=0.007,aOR=1.786,95% CI=1.172-2.723 and P=0.013,aOR=1.721,95% CI=1.123-2.638）,while genotypes of TC（rs2072407）,TC（rs734005） and CG（rs734004） decreased the risk of gastric cancer（P=0.034,aOR=0.712,95% CI=0.520-0.975;P=0.033,aOR=0.709,95% CI=0.518-0.972;and P=0.035,aOR=0.711,95% CI=0.518-0.976）.Haplotype analysis of the five SNPs showed that haplotype TCTCC reduced the risk of gastric cancer（P=0.031,aOR=0.784）;haplotype CTCTG significantly elevated the risk of gastric cancer（P=0.011,aOR=1.310）.Conclusions EZH2 variants were significantly associated with sporadic gastric cancer risk in Chinese Han population.Our results for the first time provided new insight into susceptibility factors of EZH2 gene variants in carcinogenesis of gastric cancer.