CD133基因3-UTR区域变异位点与云南汉族人群非小细胞肺癌的相关性
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摘要
目的:研究CD133基因3-UTR区域变异位点(rs2240688和rs3130)单核苷酸多态性位点(SNPs)与云南汉族人群非小细胞肺癌的相关性。方法:选取420例云南汉族非小细胞肺癌患者为病例组,588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:病例组与对照组rs2240688位点等位基因和基因型分布频率比较差异有统计学意义(P=0.013、0.033),而两组rs3130等位基因和基因型分布频率比较差异无统计学意义(P>0.05),rs2240688位点等位基因G是云南汉族非小细胞肺癌的风险性因素(OR=1.301,95%CI为1.056～1.601),rs2240688及rs3130间存在强连锁(D'>0.8);构建的两个SNPs位点的单倍型中rs2240688G-rs3130C与肺癌风险升高有关(OR=1.238,95%CI为1.003～1.528),而单倍型rs2240688T-rs3130C可能是肺癌发生的保护性因素(OR=0.828,95%CI为0.690～0.994)。结论:CD133基因3-UTR区域的SNP位点rs2240688与云南汉族人群非小细胞肺癌相关,等位基因G可能是云南汉族人群非小细胞肺癌的风险性因素。
Objective:To study the association of single nucleotide polymorphisms(SNPs,rs2240688 and rs3130) of CD133 gene in 3-UTR region mutation sites with non-small cell lung cancer in Yunnan Han population.Methods:A total of 420 patients with non-small cell lung cancer in Yunnan Han population were enrolled as the case group,and 588 healthy individuals from Yunnan Han population as the control group.The TaqMan probe genotyping method was performed to detect rs2240688 and rs3130 in the CD133 gene of the two groups.The χ2 test was used to analyze the difference between the two SNPs loci alleles,genotypes and haplotype distribution frequencies in the case group and the control group.Results:There were significant differences in the frequencies of alleles and genotypes between the case group and the control group at rs2240688(P=0.013,0.033).whereas.the differences in the frequency of rs3130 alleles and genotypes between the two groups were not significant(P>0.05).Allele G in rs2240688 was a risk factor for non-small cell lung cancer in Han population in Yunnan(OR=1.301,95% CI 1.056 ～ 1.601).There is a strong linkage between rs2240688 and rs3130(D'>0.8).rs2240688 G-rs3130 C is associated with increased risk of lung cancer(OR=1.238,95% CI 1.003 to 1.528),whereas haplotype rs2240688 T-rs3130 C may be protective for lung cancer.Sexual factors(OR=0.828,95% CI 0.690～0.994).Conclusion:The rs2240688 in the 3-UTR region of CD133 gene is associated with non-small cell lung cancer in Yunnan Han population.Allele G may be a risk factor for non-small cell lung cancer in Yunnan Han population.
Objective:To study the association of single nucleotide polymorphisms(SNPs,rs2240688 and rs3130) of CD133 gene in 3-UTR region mutation sites with non-small cell lung cancer in Yunnan Han population.Methods:A total of 420 patients with non-small cell lung cancer in Yunnan Han population were enrolled as the case group,and 588 healthy individuals from Yunnan Han population as the control group.The TaqMan probe genotyping method was performed to detect rs2240688 and rs3130 in the CD133 gene of the two groups.The χ2 test was used to analyze the difference between the two SNPs loci alleles,genotypes and haplotype distribution frequencies in the case group and the control group.Results:There were significant differences in the frequencies of alleles and genotypes between the case group and the control group at rs2240688(P=0.013,0.033).whereas.the differences in the frequency of rs3130 alleles and genotypes between the two groups were not significant(P>0.05).Allele G in rs2240688 was a risk factor for non-small cell lung cancer in Han population in Yunnan(OR=1.301,95% CI 1.056 ～ 1.601).There is a strong linkage between rs2240688 and rs3130(D'>0.8).rs2240688 G-rs3130 C is associated with increased risk of lung cancer(OR=1.238,95% CI 1.003 to 1.528),whereas haplotype rs2240688 T-rs3130 C may be protective for lung cancer.Sexual factors(OR=0.828,95% CI 0.690～0.994).Conclusion:The rs2240688 in the 3-UTR region of CD133 gene is associated with non-small cell lung cancer in Yunnan Han population.Allele G may be a risk factor for non-small cell lung cancer in Yunnan Han population.
引文
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[15]HU J L,HU X L,LU C X,et al.Variants in the 3'-untranslated region of CUL3 is associated with risk of esophageal squamous cell carcinoma[J].Journal of Cancer,2018,9(20):3647-3650.
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[19]O'BRIEN CA,AARON P,STEVEN G,et al.A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J].Nature,2007,445(7123):106-110.
[20]ERAMO A,LOTTI F,SETTE G,et al.Identification and expansion of the tumorigenic lung cancer stem cell population[J].Cell Death&Differentiation,2008,15(3):504-514.
[21]SINGH S K,CLARKE I D,TERASAKI M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Research,2003,63(18):5821-5828.
[22]HORST D,KRIEGL L,ENGEL J,et al.CD133 expression is an independent prognostic marker for low survival in colorectal cancer[J].British Journal of Cancer,2008,99(8):1285-1289.
[23]FELIX Z,REZVAN A,BENITO C,et al.Stem cell marker CD133 affects clinical outcome in glioma patients[J].Clinical Cancer Research,2008,14(1):123-129.
[24]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.
[25]MEI C,LEI Y,RONGRONG Y,et al.A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression[J].Carcinogenesis,2013,34(10):2292-2299.
[2]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.
[3]SWANTON C,GOVINDAN R.Clinical implications of genomic discoveries in lung cancer[J].The New England Journal of Medicine,2016,374(19):1864-1873.
[4]DE GROOT P,MUNDEN R F.Lung cancer epidemiology,risk factors,and prevention[J].Radiologic clinics of North America,2012,50(5):863-876.
[5]TENG Y,DING Y,ZHANG M,et al.Genome-wide haplotype association study identifies risk genes for non-small cell lung cancer[J].Journal of Theoretical Biology,2018,456:84-90.
[6]ELENA I,GIUSEPPE P.CD133:to be or not to be,is this the real question[J].American Journal of Translational Research,2013,5(6):563-581.
[7]A H Y,S M,E D Z,et al.AC133,a novel marker for human hematopoietic stem and progenitor cells[J].Blood,1997,90(12):5002-5012.
[8]CHUNXIA W,JINGPING X,JIASONG G,et al.Evaluation of CD44 and CD133 as cancer stem cell markers for colorectal cancer[J].Oncology Reports,2012,28(4):1301-1308.
[9]LIN S H,LIU T,MING X,et al.Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions[J].Scientific Reports,2016,6:21184.
[10]HUANG M,ZHU H,FENG J,et al.High CD133 expression in the nucleus and cytoplasm predicts poor prognosis in non-small cell lung cancer[J].Disease Markers,2015,2015(1):986095.
[11]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.
[12]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.
[13]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):15540-50.
[14]WANG D,WEN G M,HOU W,et al.The roles of CD133 expression in the patients with non-small cell lung cancer[J].Cancer Biomarkers,2018,22(3):1-10.
[15]HU J L,HU X L,LU C X,et al.Variants in the 3'-untranslated region of CUL3 is associated with risk of esophageal squamous cell carcinoma[J].Journal of Cancer,2018,9(20):3647-3650.
[16]DEVANNA P,VORST M V D,PFUNDT R,et al.Genome-wide investigation of an ID cohort reveals de novo3'UTR variants affecting gene expression[J].Human Genetics,2018,137(9):717-721.
[17]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.
[18]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.
[19]O'BRIEN CA,AARON P,STEVEN G,et al.A human colon cancer cell capable of initiating tumour growth in immunodeficient mice[J].Nature,2007,445(7123):106-110.
[20]ERAMO A,LOTTI F,SETTE G,et al.Identification and expansion of the tumorigenic lung cancer stem cell population[J].Cell Death&Differentiation,2008,15(3):504-514.
[21]SINGH S K,CLARKE I D,TERASAKI M,et al.Identification of a cancer stem cell in human brain tumors[J].Cancer Research,2003,63(18):5821-5828.
[22]HORST D,KRIEGL L,ENGEL J,et al.CD133 expression is an independent prognostic marker for low survival in colorectal cancer[J].British Journal of Cancer,2008,99(8):1285-1289.
[23]FELIX Z,REZVAN A,BENITO C,et al.Stem cell marker CD133 affects clinical outcome in glioma patients[J].Clinical Cancer Research,2008,14(1):123-129.
[24]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.
[25]MEI C,LEI Y,RONGRONG Y,et al.A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression[J].Carcinogenesis,2013,34(10):2292-2299.