CD133基因3-UTR区域变异位点与云南汉族人群宫颈癌的相关性
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摘要
目的:研究CD133基因3-UTR区域的(rs2240688和rs3130)单核苷酸多态性位点(SNPs)与云南汉族人群宫颈癌的相关性。方法:选取云南汉族宫颈癌患者428例作为病例组,455例云南汉族健康个体作为对照组;采用Taq Man探针基因分型方法对2组受试者CD133基因中rs2240688和rs3130位点进行基因分型,并采用χ2检验分析上述两SNPs位点等位基因、基因型及构建的单倍型分布频率在病例组与对照组中的差异。结果:rs2240688位点等位基因和基因型分布频率在病例组和对照组比较,差异具有统计学意义(P=0.019、0.040),该位点等位基因G是宫颈癌的风险性因素(OR=1.292,95%CI为1.042～1.601);而rs3130位点等位基因和基因型分布频率在病例组和对照组比较,差异无统计学意义(P>0.05);单倍型分析结果显示,单倍型rs2240688G-rs3130C是宫颈癌发生的风险性因素(P=0.023,OR=1.300,95%CI为1.037～1.630)。结论:CD133基因3-UTR区域的SNP位点rs2240688与云南汉族人群宫颈癌的发病风险相关,该位点等位基因G可能是宫颈癌发生的风险性因素。
Objective:To study the association of two single nucleotide polymorphisms(SNPs)rs2240688 and rs3130 located at 3-UTR region of CD133 gene with cervical cancer in Han population from Yunnan province.Methods:A total of 428 patients with cervical cancer in Han population in Yunnan province were enrolled as the case group,and 455 healthy individuals from Yunnan Han population as the control group.The rs2240688 and rs3130 sites in the CD133 gene were detected using using Taq Man assays.The χ2 test was used to analyze the differences in the frequency of alleles,genotypes and haplotype distribution frequency between the two SNPs in the case group and the control group.Results:The allelic and genotypic distributions of rs2240688 were significantly different between case and control groups(P=0.019 and 0.040,respectively).The allele G is a risk factor of cervical cancer(OR=1.292,95% CI:1.042～1.601).However,there is no difference of the allelic and genotypic frequencies of rs3130 between case and control groups(P>0.05).Haplotype analysis showed that The haplotype rs2240688 G-rs3130 C was associated with a high risk of cervical cancer(P=0.023,OR=1.300;95% CI:1.037～1.630).Conclusion:rs2240688 in the 3-UTR region of CD133 gene is associated with the risk of cervical cancer in Yunnan Han population.The allele G may be a risk factor for cervical cancer.
Objective:To study the association of two single nucleotide polymorphisms(SNPs)rs2240688 and rs3130 located at 3-UTR region of CD133 gene with cervical cancer in Han population from Yunnan province.Methods:A total of 428 patients with cervical cancer in Han population in Yunnan province were enrolled as the case group,and 455 healthy individuals from Yunnan Han population as the control group.The rs2240688 and rs3130 sites in the CD133 gene were detected using using Taq Man assays.The χ2 test was used to analyze the differences in the frequency of alleles,genotypes and haplotype distribution frequency between the two SNPs in the case group and the control group.Results:The allelic and genotypic distributions of rs2240688 were significantly different between case and control groups(P=0.019 and 0.040,respectively).The allele G is a risk factor of cervical cancer(OR=1.292,95% CI:1.042～1.601).However,there is no difference of the allelic and genotypic frequencies of rs3130 between case and control groups(P>0.05).Haplotype analysis showed that The haplotype rs2240688 G-rs3130 C was associated with a high risk of cervical cancer(P=0.023,OR=1.300;95% CI:1.037～1.630).Conclusion:rs2240688 in the 3-UTR region of CD133 gene is associated with the risk of cervical cancer in Yunnan Han population.The allele G may be a risk factor for cervical cancer.
引文
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[25]CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in China,2015[J].CA:A Cancer Journal for Clinicians,2016,66(2):115-132.
[2]TYAGI A,VISHNOI K,MAHATA S,et al.Cervical cancer stem cells selectively overexpress hpv oncoprotein E6 that controls stemness and self-renewal through upregulation of HES1[J].Clinical Cancer Research:an official Journal of the American Association for Cancer Research,2016,22(16):4170-4184.
[3]YUANYAN W,YIZHOU J,FEI Z,et al.Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(17):6829-6834.
[4]JANG J W,SONG Y,KIM S H,et al.CD133 confers cancer stem-like cell properties by stabilizing EGFR-AKTsignaling in hepatocellular carcinoma[J].Cancer letters,2017,389:1-10.
[5]LIU C,LI Y,XING Y,et al.The interaction between cancer stem cell marker CD133 and src protein promotes focal adhesion kinase(FAK)phosphorylation and cell migration[J].Journal of Biological Chemistry,2016,291(30):15540-15550.
[6]GERMANA R,FARGEAS C A,LE T T,et al.Letter to the Editor:an intriguing relationship between lipid droplets,cholesterol-binding protein CD133 and Wnt/β-Catenin signaling pathway in carcinogenesis[J].Stem Cells,2015,33(4):1366-1370.
[7]LIU C T,XIN Y,TONG C Y,et al.Production of interleukin-4 in CD133+cervical cancer stem cells promotes resistance to apoptosis and initiates tumor growth[J].Molecular Medicine Reports,2016,13(6):5068-5076.
[8]SHI Y Y,HE L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell Research,2005,15(2):97-98.
[9]LI Z,ZHANG Z,HE Z,et al.A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers:update of the SHEsis(http://analysis.bio-x.cn)[J].Cell Research,2009,19(4):519-523.
[10]HU N,WANG C,NG D,et al.Genomic characterization of esophageal squamous cell carcinoma from a highrisk population in China[J].Cancer Research,2009,69(14):5908-5917.
[11]FENG B J,HUANG W,SHUGART Y Y,et al.Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4[J].Nature Genetics,2002,31(4):395-399.
[12]PETERSEN S,ANINAT-MEYER M,SCHLUNS K,et al.Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung[J].British Journal of Cancer,2000,82(1):65-73.
[13]JANIKOVA M,SKARDA J,DZIECHCIARKOVA M,et al.Identification of CD133+/nestin+putative cancer stem cells in non-small cell lung cancer[J].Biomedical Papers of the Medical Faculty of the University Palacky,Olomouc,Czechoslovakia,2010,154(4):321-326.
[14]CHEN Y L,LIN P Y,MING Y Z,et al.The effects of the location of cancer stem cell marker CD133 on the prognosis of hepatocellular carcinoma patients[J].BMCCancer,2017,17(1):474.
[15]REN F,SHENG W Q,DU X.CD133:a cancer stem cells marker,is used in colorectal cancers[J].World Journal of Gastroenterology,2013,19(17):2603-2611.
[16]KWAN HO T,STEPHANIE M,TERENCE K L,et al.CD133(+)liver tumor-initiating cells promote tumor angiogenesis,growth,and self-renewal through neurotensin/interleukin-8/CXCL1 signaling[J].Hepatology,2012,55(3):807-820.
[17]PARK E K,LEE J C,PARK J W,et al.Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53[J].Cell Death&Disease,2015,6(11):e1964.
[18]ZHANG L,YANG C S,VARELAS X,et al.Altered RNA editing in 3'UTR perturbs microRNA-mediated regulation of oncogenes and tumor-suppressors[J].Scientific Reports,2016,6:23226.
[19]MA T,LIU X,CEN Z,et al.MicroRNA-302b negatively regulates IL-1βproduction in response to MSU crystals by targeting IRAK4 and Eph A2[J].Arthritis Research&Therapy,2018,20(1):34.
[20]VISHNOI A,RANI S.MiRNA biogenesis and regulation of diseases:an overview[J].Methods in Molecular Biology,2017,1509:1-10.
[21]LIU Q F,ZHANG Z F,HOU G J,et al.Polymorphisms of the stem cell marker gene CD133 and the risk of lung cancer in chinese population[J].Lung,2016,194(3):393-400.
[22]WANG Q,LIU H,XIONG H,et al.Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer[J].Molecular Carcinogenesis,2015,54(6):449-458.
[23]ARAVANTINOS G,ISAAKIDOU A,KARANTANOS T,et al.Association of CD133 polymorphisms and response to bevacizumab in patients with metastatic colorectal cancer[J].Cancer Biomarkers,2015,15(6):843-850.
[24]XU Y,ZHAO S,CUI M,et al.Down-regulation of microRNA-135b inhibited growth of cervical cancer cells by targeting FOXO1[J].International Journal of Clinical and Experimental Pathology,2015,8(9):10294-10304.
[25]CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in China,2015[J].CA:A Cancer Journal for Clinicians,2016,66(2):115-132.