miR-21基因单核苷酸多态性与宫颈癌遗传易感的关联研究  

Association analysis between the mi R-21 polymorphism and risk for cervical cancer

作　　者：林碧华[1,2] 陈婧[3] 方炳雄 余海波[5] 张鑫[1,2] 周克元[1,2] 

机构地区：[1]广东医学院生物化学与分子生物学教研室,广东东莞523808 [2]广东省医学分子诊断重点实验室,广东东莞523808 [3]东莞市人民医院药学部,广东省523059 [4]普宁市人民医院检验科,广东省515300 [5]广东医学院招投标中心,广东东莞523808

出　　处：《中华临床医师杂志（电子版）》2015年第10期72-76,共5页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金面向资助项目(81272434);湛江市科技攻关计划(2013B01091);广东医学院青年基金(Q2012005)

摘　　要：目的探讨广东地区汉族妇女mi R-21(rs1292037及rs13137)基因多态性与宫颈癌遗传易感的关系,为宫颈癌的预防和治疗提供新的思路。方法利用聚合酶链式反应-连接酶检测反应(PCR-LDR)技术,对103例宫颈癌患者和214名健康对照个体的mi R-21(rs1292037及rs13137)基因多态位点进行分型。采用非条件逻辑回归分析统计该多态位点与宫颈癌易感的相关性。利用癌症基因组图谱计划(TCGA)中宫颈癌数据,分析mi R-21在宫颈癌组织中表达、基因组变异及启动子甲基化水平。结果 HPV感染在病例组中的分布频率(87.3%)显著高于正常对照组(15.9%,P<0.001),提示HPV感染是广东地区宫颈癌发病的重要危险因素。等位基因分析结果显示,mi R-21rs1292037 T等位基因与mi R-21 rs13137 G等位基因在病例组中的分布频率与正常对照组相近,差异无统计学意义(P=0.788及P=0.690)。TCGA分析结果显示,mi R-21在宫颈癌组织中高表达,并与基因组变异无关,而可能为mi R-21启动子甲基化水平降低导致。结论 HPV感染与mi R-21高表达是宫颈癌临床表现并可能参与了宫颈癌的发生发展,但mi R-21(rs1292037 and rs13137)基因多态性与广东地区汉族妇女宫颈癌的遗传易感可能无密切关系。Objective To investigate the relationship between the miR-21 （rs1292037 and rs13137） polymorphism and the risk for cervical cancer in ethnic Hart Cantonese population. Methods The genotypes of the miR-21 （rs 1292037 and rs 13137） polymorphism were determined in 103 cervical cancer patients and 214 healthy female blood donors by polymerase chain reaction-based ligase detection reaction （PCR-LDR）. Association between the polymorphism and the risk for cervical cancer was evaluated using unconditional Logistic regression analysis. The cervical cancer data were analyzed in The Cancer Genome Atlas （TCGA）, including miR-21 expressed level, copy number variation, and DNA methylation of the promoter. Results The incidence of HPV infection in the patients （87.3%） was much higher than that in the control subjects （15.9%, P〈0.001）, implying HPV infection as a critical risk factor for cervical cancer development in our study population. The T allele of miR-21 rs1292037 and the G allele of rrdR-21 rsl3137 polymorphism in the cases was similar to controls （P=0.788, P=0.690 respectively）, suggesting that there two alleles might not effect on cervical cancer development or effect on miR-21 expression. The TCGA analyzed showed that miR-21 was upregulated in cervical cancer tissues, but the copy number variation of miR-21 didn＇t change significantly. Furthermore, the DNA methylation was downregulated in the promoter of miR-21 which might increase miR-21 level in cervical cancer tissues. Conclusion The HPV infection and overexpressed miR-21 might contribute cervical cancer development and progression, but the miR-21 （rs1292037 and rs13137） polymorphism may not play a role in cervical cancer susceptibility in ethnic Han Cantonese population.

关 键 词：多态性 单核苷酸 宫颈肿瘤 MI R-21 rs1292037 rs13137 

分 类 号：R737.33[医药卫生—肿瘤]