MIR17HG基因多态与食管鳞癌发病风险的关联研究

Association of MIR17HG polymorphisms with the risk of esophageal squamous cell carcinoma

目的探讨miR-17-92基因簇宿主基因(microRNA 17-92 cluster host gene,MIR17HG)单核苷酸多态性(single nucleotide polymorphisms,SNPs)与食管鳞癌(esophageal squamous cell carcinoma,ESCC)发病风险的关联。方法选取2014年10月至2018年12月河南省林州市肿瘤医院确诊的437例ESCC患者为病例组,选取同期在当地医院参加筛查项目的490名健康者为对照组。采用MassArray时间飞行质谱生物芯片检测MIR17HG区域中SNPs位点(rs17735387、rs4284505、rs9589207和rs72631821)基因型,并对各位点与ESCC发病风险进行关联分析。结果rs4284505(A/G)与ESCC发病风险相关。经多因素校正后,与rs4284505AA基因型携带者相比,AG基因型携带者发生ESCC风险增加(调整OR=1.548,95%CI:1.085~2.210,P=0.016);显性模型提示rs4284505AG/GG基因型携带者罹患ESCC的风险是AA基因型携带者的1.465倍(95%CI:1.040~2.065,P=0.029)。分层分析显示,在男性及吸烟亚组中,rs4284505AG基因型相比于AA基因型增加ESCC的发病风险。交互作用分析表明,与rs4284505AA基因型且不吸烟者相比,AG基因型且吸烟者更易患ESCC(OR=4.218,95%CI:2.135~8.333,P<0.001)。结论MIR17HG区域的SNP位点rs4284505与ESCC发病风险相关,其突变型G等位基因携带者罹患ESCC的风险高于野生型A等位基因携带者。

Objective To evaluate the association between single nucleotide polymorphisms(SNPs)of microRNA 17-92 cluster host gene(MIR17HG)and the risk of esophageal squamous cell carcinoma(ESCC).Methods In this study,437 unrelated ESCC patients and 490 healthy controls were recruited from Linzhou Cancer Hospital between October 2014 and December 2018.Four SNPs in MIR17HG(rs17735387,rs4284505,rs9589207 and rs72631821)were genotyped using the Sequenom MassArray platform.And the associations between the SNPs and the ESCC were analyzed.Results It was showed that rs4284505(A/G)was significantly correlated with ESCC susceptibility.Individuals carrying rs4284505AG(adjusted OR=1.548,95%CI:1.085-2.210,P=0.016)and AG/GG(adjusted OR=1.465,95%CI:1.040-2.065,P=0.029)genotypes showed a significantly increased risk for ESCC compared with individuals carrying the AA genotype after adjustment for age,gender and smoking status.No statistically significant association between the haplotypes(containing two polymorphisms rs17735387and rs4284505)and ESCC risk was observed.Stratified analyses showed that rs4284505AG had more striking effects on increasing ESCC risk in males(adjusted OR=1.633,95%CI:1.041-2.562,P=0.033)and smokers(adjusted OR=1.941,95%CI:1.090-3.457,P=0.024).SNP-smoking interaction analysis also indicated that the association between rs4284505 and ESCC risk could be increased by smoking status.Smoking subjects who carried the rs4284505AG genotypes had a remarkably increased risk for ESCC(OR=4.218,95%CI:2.135-8.333,P<0.001),compared with those having wild-type genotypes and nonsmoking history.Conclusions A genetic variant in MIR17HG(rs4284505)may be an important genetic determinant of ESCC susceptibility in the Chinese population.