云南省汉族人群CD25基因多态性与宫颈癌的发生发展的相关性The Correlation between Polymorphisms in CD25 Gene and Initiation and Development of Cervical Cancer in Yunnan Han Population
严志凌,杨宏英,张红平,尹春梅,张芍,李文亮,李传印,史荔,杨谢兰
YAN Zhiling,YANG Hongying,ZHANG Hongping,YIN Chunmei,ZHANG Shao,LI Wenliang,Li Chanyin,SHI Li,YANG Xielan
摘要(Abstract):
目的:探讨CD25基因多态性与云南汉族人群宫颈癌发生发展的相关性。方法:选取云南地区汉族人群癌前病变(CIN)患者136例,宫颈癌患者227例以及汉族健康体检人群483例,采用Taq Man探针基因分型方法对CD25基因中SNP位点rs7072793(C>T)和rs3118470(C>T)进行基因分型,研究其等位基因、基因型及所构建的单倍型在CIN患者、宫颈癌患者和健康对照人群中分布频率。结果:rs7072793(C>T)等位基因C和T在CIN组和对照组、CIN组与癌症组中分布频率的差异具有统计学意义(P=0.039和0.039),提示该位点等位基因C在宫颈癌发生和发展阶段分别发挥保护(OR=0.75;95%CI∶0.57~0.99)和风险因素(OR=1.38;95%CI∶1.02~1.86);rs3118470(G>T)的等位基因C和T在CIN组和对照组、CIN组和癌症组中分布频率的差异具有统计学意义(P<0.001和P<0.001),提示该位点等位基因C在宫颈癌发生和发展阶段分别发挥保护(OR=0.576;95%CI∶0.436~0.762)和风险因素(OR=1.750;95%CI∶1.283~2.388)。结论:CD25基因中多态性位点rs7072793(C>T)和rs3118470(C>T)的等位基因C是宫颈癌发生的保护性因素和宫颈癌发展过程中的风险因素。
Objective: To investigate the correlation of CD25 gene polymorphism with the occurrence and development of cervical cancer in a Yunnan Han population. Methods: A total of 136 patients with CIN,227 patients with cervical cancer and 483 healthy individuals were recruited in this study.Taq Man probe genotyping was adopted to analyze the genotypes of SNP locus rs7072793( C > T) and rs3118470( C > T) of CD25 gene and to research the frequencies of the alleles,genotypes and haplotypes in CIN patients,cervical cancer patients and healthy controls. Results: CIN group < cancer group < control group in terms of C allele frequency distribution of rs7072793( C > T) and CIN group >cancer group > control group in terms of T allele frequency distribution of rs7072793( C > T),the differences were statistically significant( P < 0. 05). The allele C of rs7072793( C > T) was a protective factor in stage of initiation of cervical cancer( OR = 0. 75,95% CI∶ 0. 57 ~ 0. 99) and risk factor in developmental stage of cervical cancer( OR = 1. 38,95% CI∶ 1. 02 ~ 1. 86). CIN group < cancer group or control group in terms of C allele frequency distribution of polymorphic site rs3118470( C >T) and CIN group > cancer group or control group in terms of T allele frequency distribution of polymorphic site rs3118470( C > T). There were statistically significant differences between CIN group and cancer group or control group( P < 0. 001). The allele C of rs3118470( C > T) was a protective factor in stage of initiation of cervical cancer( OR = 0. 576,95% CI∶ 0. 436 ~ 0. 762) and risk factor in developmental stage of cervical cancer( OR = 1. 750,95% CI∶ 1. 283 ~ 2. 388). Conclusion: In polymorphic sites of rs7072793( C > T) and rs3118470( C > T) of CD25 gene,C allele is protective factor of cervical cancer and risk factor in the development of cervical cancer.
关键词(KeyWords):
基因型;宫颈肿瘤;云南汉族;CD25;多态性;相关性
genotype;cervical neoplasm;Yunnan Han population;CD25;polymorphisms;correlation
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);云南省科技厅-昆明医科大学应用基础研究联合专项(201501UH01630);; 云南省肿瘤内设机构(2014NS139);; 国家自然科学基金项目(81573206);; 云南省妇科肿瘤内设机构(2014NS032,2014NS033)
作者(Author):
严志凌,杨宏英,张红平,尹春梅,张芍,李文亮,李传印,史荔,杨谢兰
YAN Zhiling,YANG Hongying,ZHANG Hongping,YIN Chunmei,ZHANG Shao,LI Wenliang,Li Chanyin,SHI Li,YANG Xielan
DOI: 10.19367/j.cnki.1000-2707.2017.04.001
参考文献(References):
- [1]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA:a cancer journal for clinicians,2015(2):87-108.
- [2]Hildesheim A,Wang SS.Host and viral genetics and risk of cervical cancer:a review[J].Virus Research,2002(2):229-240.
- [3]Yao Y,Huang W,Yang X,et al.HPV-16 E6 and E7protein T cell epitopes prediction analysis based on distributions of HLA-A loci across populations:an in silico approach[J].Vaccine,2013(18):2289-2294.
- [4]Xiao X,Liu L,Li WJ,et al.HLA-A,HLA-B,HLA-DRB1 polymorphisms and risk of cervical squamous epithelial cell carcinoma:a population study in China[J].Asian Pacific Journal of Cancer Prevention:APJCP,2013(7):4427-4433.
- [5]Bohling SD,Allison KH.Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes:a potential therapeutic target[J].Modern pathology:an official journal of the United States and Canadian Academy of Pathology,2008(12):1527-1532.
- [6]Zheng J,Yu X,Jiang L,et al.Association between the Cytotoxic T-lymphocyte antigen 4+49G>A polymorphism and cancer risk:a meta-analysis[J].BMC cancer,2010(5):122-127.
- [7]Bach JF.Regulatory T cells under scrutiny[J].Nature Reviews Immunology,2003(3):189-198.
- [8]von Herrath MG,Harrison LC.Antigen-induced regulatory T cells in autoimmunity[J].Nature Reviews Immunology,2003(3):223-232.
- [9]Bouzid D,Amouri A,Fourati H,et al.Polymorphisms in the IL2RA and IL2RB genes in inflammatory bowel disease risk[J].Genetic Testing and Molecular Biomarkers,2013(11):833-839.
- [10]Abdelrahman HM,Sherief LM,Abd Elrahman DM,et al.The association of PTPN22(rs2476601)and IL2RA(rs11594656)polymorphisms with T1D in Egyptian children[J].Human Immunology,2016(8):682-686.
- [11]Li H,Zhou H,Zhang Q,et al.Functional polymorphism rs7072793 C>T affect individual susceptibility to breast cancer by modulating CD25 transcription activity[J].Molecular Carcinogenesis,2013(5):370-376.
- [12]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(4):519-523.
- [13]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.
- [14]Sole X,Guino E,Valls J,et al.SNPStats:a web tool for the analysis of association studies[J].Bioinformatics,2006(15):1928-1929.
- [15]Wang RF.Regulatory T cells and innate immune regulation in tumor immunity[J].Springer Seminars in Immu Nopathology,2006(1):17-23.
- [16]Suri-Payer E,Amar AZ,Thornton AM,et al.CD4+CD25+T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells[J].Journal of Immunology(Baltimore,Md:1950),1998(3):1212-1218.
- [17]Hou F,Ma D,Cui B.Treg cells in different forms of uterine cancer[J].International Journal of Clinical Chemistry,2013(4):337-340.
- [18]Clark CE,Hingorani SR,Mick R,et al.Dynamics of the immune reaction to pancreatic cancer from inception to invasion[J].Cancer Research,2007(19):9518-9527.
- [19]Visser J,Nijman HW,Hoogenboom BN,et al.Frequencies and role of regulatory T cells in patients with(pre)malignant cervical neoplasia[J].Clinical and Experimental Immunology,2007(2):199-209.
- [20]Piersma SJ,Jordanova ES,van Poelgeest MI,et al.High number of intraepithelial CD8+tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer[J].Cancer Research,2007(1):354-361.
- [21]Kobayashi M,Abiru N,Arakawa T,et al.Altered B:9-23 insulin,when administered intranasally with cholera toxin adjuvant,suppresses the expression of insulin autoantibodies and prevents diabetes[J].Journal of Immunology,2007(4):2082-2088.
- [22]Onizuka S,Tawara I,Shimizu J,et al.Tumor rejection by in vivo administration of anti-CD25(interleukin-2receptor alpha)monoclonal antibody[J].Cancer Research,2009(13):3128-3133.
- [23]Shimizu J,Yamazaki S,Sakaguchi S.Induction of tumor immunity by removing CD25+CD4+T cells:a common basis between tumor immunity and autoimmunity[J].Journal of Immunology(Baltimore,Md:1950),2099(10):5211-5218.
- [24]Yu P,Lee Y,Liu W,et al.Intratumor depletion of CD4+cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors[J].The Journal of Experi Mental Medicine,2005(5):779-791.
- [25]Steitz J,Bruck J,Lenz J,et al.Depletion of CD25(+)CD4(+)T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon alpha-induced,CD8(+)T-cell-dependent immune defense of B16 melanoma[J].Cancer Research,2001(24):8643-8646.
- [26]Marshall NA,Vickers MA,Barker RN.Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1[J].Journal of Immunology,2003(12):6183-6189.
- [27]Suvas S,Azkur AK,Kim BS,et al.CD4+CD25+regulatory T cells control the severity of viral immunoinflammatory lesions[J].Journal of Immunology,2004(7):4123-4132.
- [28]Cabrera R,Tu Z,Xu Y,et al.An immunomodulatory role for CD4(+)CD25(+)regulatory T lymphocytes in hepatitis C virus infection[J].Hepatology,2004(5):1062-1071.
- [29]Fichna M,Zurawek M,Fichna P,et al.Polymorphic variants of the IL2RA gene and susceptibility to type 1 diabetes in the Polish population[J].Tissue Antigens,2012(3):198-203.
文章评论(Comment):
|
||||||||||||||||||
|