云南汉族人群CD40基因多态性与肺癌发生发展的相关性The Correlation of CD40 Gene Polymorphisms with the Initiation and Development of Lung Cancer in Yunnan Han Population
王小娜,张禹,王培智,周紫云,高雪,杨勤兴,刘舒媛,李传印,史荔,姚宇峰
WANG Xiaona,ZHANG Yu,WANG Peizhi,ZHOU Ziyun,GAO Xue,YANG Qinxing,LIU Shuyuan,LI Chuanyin,SHI Li,YAO Yufeng
摘要(Abstract):
目的:探讨CD40基因多态性与云南汉族人群肺癌发生发展的相关性。方法:选取云南地区汉族人群肺癌Ⅰ+Ⅱ期患者151例、Ⅲ+Ⅳ期患者316例,同时选择云南地区汉族健康体检人群384例(对照组),采用Taq Man探针基因分型方法对两组被检者CD40基因中rs1883832(C>T)和rs4810485(G>T)2个多态性位点进行基因分型,观察等位基因、基因型及所构建的单倍型在肺癌Ⅰ+Ⅱ期患者、肺癌Ⅲ+Ⅳ期患者和对照组的分布频率。结果:rs4810485位点等位基因G和T在Ⅲ+Ⅳ期肺癌和对照组被检者的分布频率差异具有统计学意义(P=0.013);遗传模式的分析结果经年龄校正后,rs1883832位点在Dominant模式下CC基因型和CT~TT基因型在Ⅰ+Ⅱ期及Ⅲ+Ⅳ期肺癌患者分别与对照组的分布频率比较,差异具有统计学意义(P=0.011和0.008);rs4810485位点在Dominant模式下基因型GG和基因型GT~TTde分布频率比较亦具有统计学意义(P=0.008和0.001)。结论:CD40基因中多态性位点rs4810485位点等位基因G和基因型GG可能是肺癌发生的风险性因素,而rs1883832位点基因型CC可能是肺癌发生的风险因素。
Objective: To investigate the correlation of the single nucleotide polymorphisms( SNPs)( rs1883832 C > T and rs4810485 G > T) in CD40 gene with the occurrence and development of lung cancer in a Yunnan Han population. Methods: A total of 155 lung cancer patients in pathological stages Ⅰ + Ⅱ,316 lung cancer patients in pathological stages Ⅲ + Ⅳ and 384 healthy individuals were recruited in this study. The genotypes of 2 polymorphism loci( rs1883832 C > T and rs4810485 G > T)of CD40 gene were analyzed by Taqman assay. The distribution frequencies of allele,genotype,and haplotypes in lung cancer patients of pathological stages of Ⅰ + Ⅱ and Ⅲ + Ⅳ,and normal control were observed. Results: The allelic frequencies of G and T at locus rs4810485 in group Ⅲ + Ⅳ were significantly different from those in control group( P = 0. 013),suggesting G at the locus of the allele was the risk factor( OR = 1. 33,95% CI: 1. 06 ~ 1. 66). The analysis results of inheritance mode showed that under Dominant mode( best fit mode),at locus rs1883832,there were significant differences of frequencies of genotypes CC and CT ~ TT between Ⅰ + Ⅱ and control,and between Ⅲ + Ⅳand control group( P = 0. 011 and 0. 008). In regard of locus rs4810485,under Dominant mode,the distribution frequncies of genotypes of GG and GT ~ TTde were significantly different between Ⅰ + Ⅱand control,and between Ⅲ + Ⅳ and control group( P = 0. 008 和 0. 001). Conclusions: At polymorphism locus rs4810485 of gene CD40,allele G( OR = 1. 33,95% CI: 1. 06 ~ 1. 66) and genotype GG( OR = 1. 79,95% CI: 1. 17 ~ 2. 74) might be the risk factors of occurrence of lung cancer. While at locus rs1883832,genotype CC be the risk factor of lung cancer initiation( OR = 1. 73,95% CI: 1. 13 ~2. 63).
关键词(KeyWords):
基因型;肺肿瘤;相关性;云南;CD40
genotype;lung neoplasm;correlation;Yunnan;CD40
基金项目(Foundation): 云南省医学学科带头人培养计划(D-201669);; 云南省科技厅-昆明医科大学应用基础研究联合专项(2013FB064);; 云南省肿瘤内设机构(2014NS139)
作者(Author):
王小娜,张禹,王培智,周紫云,高雪,杨勤兴,刘舒媛,李传印,史荔,姚宇峰
WANG Xiaona,ZHANG Yu,WANG Peizhi,ZHOU Ziyun,GAO Xue,YANG Qinxing,LIU Shuyuan,LI Chuanyin,SHI Li,YAO Yufeng
DOI: 10.19367/j.cnki.1000-2707.2017.04.003
参考文献(References):
- [1]Mc Guire S.International agency for research on Cancer,WHO press,2015[J].Advances in nutrition,2016(2):418-419.
- [2]Li Y,Yao Y,Qian X,et al.The association of adiponectin gene promoter variations with non-small cell lung cancer in a Han Chinese population[J].Plo S One,2015(5):e0127751.
- [3]van Kooten C,Banchereau J.CD40-CD40 ligand[J].Journal of Leukocyte Biology,2000(1):2-17.
- [4]Tong AW,Stone MJ.Prospects for CD40-directed experimental therapy of human cancer[J].Cancer Gene Therapy,2003(1):1-13.
- [5]Lo SS,Wu CW,Chi CW,et al.High CD40 expression in gastric cancer associated with expanding type histology and liver metastasis[J].Hepato-Gastroenterology,2005(66):1902-1904.
- [6]Ishikawa K,Miyamoto M,Yoshioka T,et al.Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis[J].Cancer,2008(3):530-541.
- [7]Dolen Y,Yilmaz G,Esendagli G,et al.CD40-1C>T single nucleotide polymorphism and CD40 expression on breast tumors[J].Cytokine,2010(3):243-244.
- [8]Chen JM,Guo J,Wei CD,et al.The association of CD40 polymorphisms with CD40 serum levels and risk of systemic lupus erythematosus[J].BMC,2015(121):525-528.
- [9]Tang W,Xue L,Yan Q,et al.Association of Single Nucleotide Polymorphisms in the Apoptosis-Related Genes TP63 and CD40 with Risk for Lung Cancer in a Chinese Han Population[J].The Tohoku Journal of Experimental Medicine,2016(4):279-286.
- [10]Shi YY,He L.SHEsis,a powerful software platform for analyses of linkage disequilibrium,haplotype construction,and genetic association at polymorphism loci[J].Cell Research,2005(2):97-98.
- [11]Sole X,Guino E,Valls J,et al.SNPStats:a web tool for the analysis of association studies[J].Bioinformatics,2006(15):1928-1929.
- [12]Lu YT,Sun XJ,Chen C,et al.Role of PI3K-AKT signaling pathway in CD40-mediated proliferation and invasiveness of lung cancer cell[J].Cytokine,2013(10):775-779.
- [13]Lu XD,Zhu XL,Chen C,et al.Inhibition of lung cancer cell proliferation by CD40 signaling through tumor necrosis factor I[J].Chinese Journal of Cancer,2009(1):20-23.
- [14]Xie F,Shi Q,Wang Q,et al.CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma[J].Journal of Neuroimmunology,2010(1):62-69.
- [15]Chen P,Zhu J,Liu DY,et al.Over-expression of survivin and VEGF in small-cell lung cancer may predict the poorer prognosis[J].Medical Oncology,2014(1):775.
- [16]Wu CJ,Guo J,Luo HC,et al.Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus[J].Rheumatology International,2016(1):45-52.
- [17]Chen X,Hu Z,Li W,et al.Synergistic combined effect between CD40-1C>Tand CTLA-4+6230G>A polymorphisms in Graves'disease[J].Gene,2015(2):154-158.
- [18]Lee,Zhou G,Wang Y,et al.CD40-1C>T polymorphism and the risk of lung cancer in a Chinese population[J].International Journal of Clinical and Experimental Pathology,2015(11):15163-15169.
- [19]Roman-Fernandez IV,Avila-Castillo DF,CerpaCruz S,et al.CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico[J].Genetics and Molecular Research:GMR,2016(4):560.
- [20]Chen F,Hou S,Jiang Z,et al.CD40 polymorphisms in Han Chinese patients with Fuch uveitis syndrome[J].Molecular Vision,2011(17):2469-2472.
- [21]Wang M,Li Y,Li W,et al.The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary syndrome in a Chinese case-control study[J].DNA and Cell Biology,2011(3):173-178.
- [22]Yun Y,Ma C,Ma X.The SNP rs1883832 in CD40 gene and risk of atherosclerosis in Chinese population:a meta-analysis[J].Plo S One,2014(5):e97289.
- [23]Inal EE,Rustemoglu A,Inanir A,et al.Associations of rs4810485 and rs1883832 polymorphisms of CD40 gene with susceptibility and clinical findings of Behcet's disease[J].Rheumatology International,2015(5):837-843.
- [24]Shuang C,Dalin L,Weiguang Y,et al.Association of CD40 gene polymorphisms with sporadic breast cancer in Chinese Han women of Northeast China[J].Plo S One,2011(8):e23762.
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