miR-17-92启动子区基因多态性与子宫内膜癌易感性及预后的相关性

Association between polymorphisms in the promoter region of the miR-17-92 cluster and endometrial cancer

目的探讨miR-17-92基因启动子区基因多态性与子宫内膜癌(EC)易感性及预后的关系。方法应用聚合酶链反应-连接酶反应检测398例EC患者与420例健康人群miR-17-92基因簇启动子区rs1813389A/G、rs9515692C/T两个单核苷酸多态性(SNP)位点的基因型,并分析两个位点SNP与EC发病和预后的相关性。结果与携带rs1813389AA基因型者相比,GG基因型显著降低EC的发病风险(OR=0.49,95%CI=0.32~0.78,P=0.002),与A等位基因携带者相比,G等位基因显著降低EC的发病风险(OR=0.75,95%CI=0.62~0.91,P=0.005);与携带rs9515692CC基因型者相比,TT基因型可显著降低EC发病风险(OR=0.53,95%CI=0.34~0.82,P=0.004),与C等位基因的携带者相比,T等位基因可降低EC的发病风险(OR=0.77,95%CI=0.63~0.94,P=0.010)。预后分析显示rs1813389AG或GG基因型是EC患者预后的独立影响因素(HR=0.49,95%CI=0.36~0.82,P=0.007;HR=0.29,95%CI=0.16~0.83,P=0.017)。结论miR-17-92基因簇启动子区rs1813389A/G、rs9515692C/T多态性可能成为中国华北地区女性EC发病和预后判断的分子标志物。

Objective:To investigate the relationship between the polymorphism of miR-17-92 and the susceptibility and prognosis of endometrial cancer(EC)in northern Chinese women.Methods:Through case-control study,polymerase chain reaction and ligase detection reaction(PCR-LDR)was used to detect the polymorphism of rs1813389A/G and rs9515692C/T in miR-17-92 promoter region of 398 cases of EC and 420 healthy control subjects,and to analyze the correlation between the two SNPS and the incidence and prognosis of EC.Results:Compared with rs1813389AA genotype carriers,GG genotype significantly reduced the risk of EC(OR=0.49,95%CI=0.32~0.78,P=0.002).Compared with carriers of allele A,the G allele significantly reduced the risk of EC(OR=0.75,95%CI=0.62~0.91,P=0.005).Compared with rs9515692CC genotype carriers,TT genotype significantly reduced the risk of EC(OR=0.53,95%CI=0.34~0.82,P=0.004).Compared with carriers of the C allele,the T allele decreased the risk of developing EC(OR=0.77,95%CI=0.63~0.94,P=0.010).Prognostic analysis showed that rs1813389 AG or GG genotypes were independent factors influencing the prognosis of EC patients(HR=0.49,95%CI=0.36~0.82,P=0.007;HR=0.29,95%CI=0.16~0.83,P=0.017).Conclusion:Rs1813389A/G and rs9515692C/T polymorphisms in the promoter region of the miR-17-92 cluster may be a molecular marker for the diagnosis of EC morbidity and prognosis in northern Chinese women.