高分辨率溶解曲线分析miRNA-196a2基因多态性与肺癌相关性
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摘要
目的探讨microRNA-196a2基因多态性(rs1614913)与中国人群肺癌发病相关性。方法应用高分辨率溶解曲线(high resolution melting,HRM)分析技术对32例肺癌患者、27例肺部良性肿瘤患者及84例健康个体的microRNA-196a2基因多态性进行分析,并采用聚合酶链反应-限制性片段长度多态性(PCR-restriction fragment length polymorphism,PCRRFLP)技术加以佐证。结果 micro-196a2在各组基因型分布均达到Hardy-Weinberg平衡。肺癌组C等位基因的分布频率高于对照组(P=0.0016),OR=2.592(95%CI1.424~4.716),说明C等位基因增加肺癌患病风险。结论 MicroRNA-196a2T/C(rs1614913)多态性增加肺癌的发病风险。MicroRNA-196a2基因多态性rs1614913可能是肺癌的一种有效的遗传标记物。
Objective To investigate the effect of the microRNA-1962 gene polymorphism on risk of lung cancer.MethodsThirty-two patients with lung cancer,27 patients with benign neoplasm in lung and 84 healthy controls.All subjects were genotyped for the microRNA-196a2 SNP by high resolution melting analysis,and the results were supported by PCR-restriction fragment length polymorphism method.Results The microRNA 1962 agenotype distribution among three group was in Hardyweinberg equilibrium.The frequency of the C allele in group of lung cancer was higher than that of the control group(P=0.0016).The odds ratio 2.592(95% CI 1.424~4.716)suggested an association of the C allele with increased risk of lung cancer.Conclusions The microRNA-196a2T/C polymorphism(rs1614913)is associated with an increased risk of lung cancer.The miRNA-196a2 functional polymorphism rs11614913 might be an effective genetic marker for lung cancer.
Objective To investigate the effect of the microRNA-1962 gene polymorphism on risk of lung cancer.MethodsThirty-two patients with lung cancer,27 patients with benign neoplasm in lung and 84 healthy controls.All subjects were genotyped for the microRNA-196a2 SNP by high resolution melting analysis,and the results were supported by PCR-restriction fragment length polymorphism method.Results The microRNA 1962 agenotype distribution among three group was in Hardyweinberg equilibrium.The frequency of the C allele in group of lung cancer was higher than that of the control group(P=0.0016).The odds ratio 2.592(95% CI 1.424~4.716)suggested an association of the C allele with increased risk of lung cancer.Conclusions The microRNA-196a2T/C polymorphism(rs1614913)is associated with an increased risk of lung cancer.The miRNA-196a2 functional polymorphism rs11614913 might be an effective genetic marker for lung cancer.
引文
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[2]Hongbin J,Danan L,Liang C,et al.The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies[J].Cancer Cell,2006,9(6):485-495.
[3]Mahoney C,Choudhury B H,Edkins S,et al.LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition[J].British Journal of Cancer,2009,100(2):370-375.
[4]To M D,Wong C E,Karnezis A N,et al.Kras regulatory elements and exon 4Adetermine mutation specificity in lung cancer[J].Nature Genetics,2008,40(10):1240-1244.
[5]Hatanaka H.Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer[J].Nature,2007,448(7153):561-566.
[6]Paez JG,Janne PA,Lee JC,et al.EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy[J].Science,2004,304(5676):1497-1500.
[7]Shaw AT,Yeap BY,Solomon BJ,et al.Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement:a retrospective analysis[J].Lancet Oncology,2011,12(11):1004-1012.
[8]Rodrigo A,Bengt B,Ariane D,et al.Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer[J].New England Journal of Medicine,2004,350(4):351-360.
[9]Siegel R L,Fedewa S A,Miller K D,et al.Cancer statistics for Hispanics/Latinos,2015[J].Ca A Cancer Journal for Clinicians,2015,65(6):457-480.
[10]Kim N.Regulation of microRNA biogenesis[J].Nature Reviews Molecular Cell Biology,2014,15(8):605-610.
[11]Di Leva G,Garofalo M,Croce CM.MicroRNAs in cancer[J].Annu Rev Pathol,2014,9(1):287-314.
[12]Georges M,Charlier C.Polymorphic miRNA-mediated gene regulation:contribution to phenotypic variation and disease[J].Current Opinion in Genetics&Devolopment,2007,17(3):166-176.
[13]Xinjun H,Yi-Lin Y,April D L,et al.Observation of miRNA Gene Expression in Zebrafish Embryos by In Situ Hybridization to MicroRNA Primary Transcripts[J].Zebrafish,2011,8(1):1-8.
[14]Liu C J,Tsai M M,Tu H F,et al.miR-196aOverexpression and miR-196a2Gene Polymorphism Are Prognostic Predictors of Oral Carcinomas[J].Annals of Surgical Oncology,2013,20(3):406-414.
[15]Hofinger B J,Jing H C,Hammond-Kosack K E,et al.High-resolution melting analysis of cDNA-derived PCR amplicons for rapid and cost-effective identification of novel alleles in barley[J].Theor Appl Genet,2009,119(5):851-865.
[16]Bartel DP.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116(2):281-297.
[17]Zhi H,Wang L,Ma G,et al.Polymorphisms of miRNAs genes are associated with the risk and prognosis of coronary artery disease[J].Clinical Research in Cardiology,2012,101(4):289-296.
[18]Buraczynska M,Zukowski P,Wacinski P,et al.Polymorphism in microRNA-196a2contributes to the risk of cardiovascular disease in type 2diabetes patients[J].Journal of Diabetes&Its Complications,2014,28(5):617-620.
[19]Hoffman A E,Zheng T,Yi C,et al.microRNA miR-196a-2and breast cancer:agenetic and epigenetic association study and functional analysis[J].Cancer Res,2009,69(14):5970-5977.
[20]Zhan J F,Chen L H,Chen Z X,et al.A functional variant in MicroRNA-196a2is associated with susceptibility of colorectal cancer in a chinese population[J].Archives of Medical Research,2011,42(2):144-148.
[21]Wang N,Li Y,Zhou R M,et al.Hsa-miR-196a2functional SNP is associated with the risk of ESCC in individuals under 60years old[J].Biomarkers,2014,19(1):43-48.
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