TAP1 637A/G基因多态性与中国云南汉族鼻咽癌发病风险关系的研究
|
摘要
目的研究抗原处理相关转运体蛋白1(The transporter associated with antigen processing 1 TAP-1) 637A/G基因多态性(SNP)与中国云南汉族鼻咽癌(nasopharyngeal carcinoma, NPC)发病风险性关系,寻找鼻咽癌的易感基因。
方法应用聚合酶链反应—限制性片段长度多态性(restriction fragment length polymorphism-PCR,PCR-RFLP)对233例云南籍汉族鼻咽癌患者和296例云南籍汉族非肿瘤对照组进行TAP1 637A/G SNP检测,采用聚合酶链反应(PCR)检测鼻咽癌患者EB病毒(Epstein-Barr virus, EBV)感染状况。计算各基因型与鼻咽癌发病风险以及与鼻咽癌患者EBV感染的相关性。
结果1.233例云南鼻咽癌患者中EBV感染率为58.4%,对照组EBV感染率为42.2%,差异有统计学意义(p<0.05)。2.比较各基因型在两组中的分布：纯合子突变(GG型)、杂合子突变(AG型)和无突变者(AA型)分布差异均有统计学意义。且TAP-1637A/G多态性与鼻咽癌的发病有关,与AA基因型相比,携带GG、AG基因型罹患鼻咽癌的风险分别为4.26倍(95% CI=2.08-8.66,P<0.001)和1.56倍(95%CI=1.12-2.33；P=0.036)；至少携带637G等位基因罹患鼻咽癌的风险为1.88倍(95% CI=1.35-2.82,P<0.001)。3.TAP-1三种基因型频率在EBV阳性组与EBV阴性组间比较,差异有统计学意义。P=0.02；在EBV阳性组中至少携带637G等位基因罹患鼻咽癌的风险为2.76倍(95% CI=1.69-4.63,P<0.001),而在EBV阴性组中携带637G等位基因并不增加个体罹患鼻咽癌的风险,OR值为0.98(95%CI=0.59-1.66,P<0.001)。
结论1.TAP-1 637位点A/G基因多态性与云南汉族鼻咽癌遗传易感相关；2.TAP1基因多态性干扰HLA I抗原呈递在EBV感染致云南汉族鼻咽癌患病过程可能相关。
Objective To study the relationship between 637A/G gene polymorphisms of The transporter associated with antigen processing 1 gene and nasopharyngeal carcinomas(NPC),In order to find out the susceptible genes of nasopharyngeal carcinomas in Han population in Yunnan China.
Methods Two hundred thirty and three cases with NPC and Two hundred ninety and six cases matched cancer-free controls were genotyped for the TAP-1 637A/G polymorphism by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Epstein-Barr virus infection was detected by PCR。The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model.
Results Contrast with homozygous TAP1 637 AA, G allele significantly increasing risk of NPC was associated with homozygous 637 GG OR=4.26 (95% CI=2.08-8.66,P＜0.001) and heterozygous 637 AG OR=1.56 (95% CI=1.12-2.33; P= 0.036). The subjects at least having one TAP-1 637 G allele had OR of 1.88 (95% CI=1.35-2.82,P＜0.001). Furthermore, Smoking and EBV infection may increase the risk of developing NPC interacting with TAP1 637 A/G polymorphism.
Conclusions 1.The TAP1 637G allele is associated with the NPC in Han population in Yunnan China,2. EBV pathogenesis in NPC might be facilitated by polymorphisms in the TAP1 proteins.
方法应用聚合酶链反应—限制性片段长度多态性(restriction fragment length polymorphism-PCR,PCR-RFLP)对233例云南籍汉族鼻咽癌患者和296例云南籍汉族非肿瘤对照组进行TAP1 637A/G SNP检测,采用聚合酶链反应(PCR)检测鼻咽癌患者EB病毒(Epstein-Barr virus, EBV)感染状况。计算各基因型与鼻咽癌发病风险以及与鼻咽癌患者EBV感染的相关性。
结果1.233例云南鼻咽癌患者中EBV感染率为58.4%,对照组EBV感染率为42.2%,差异有统计学意义(p<0.05)。2.比较各基因型在两组中的分布：纯合子突变(GG型)、杂合子突变(AG型)和无突变者(AA型)分布差异均有统计学意义。且TAP-1637A/G多态性与鼻咽癌的发病有关,与AA基因型相比,携带GG、AG基因型罹患鼻咽癌的风险分别为4.26倍(95% CI=2.08-8.66,P<0.001)和1.56倍(95%CI=1.12-2.33；P=0.036)；至少携带637G等位基因罹患鼻咽癌的风险为1.88倍(95% CI=1.35-2.82,P<0.001)。3.TAP-1三种基因型频率在EBV阳性组与EBV阴性组间比较,差异有统计学意义。P=0.02；在EBV阳性组中至少携带637G等位基因罹患鼻咽癌的风险为2.76倍(95% CI=1.69-4.63,P<0.001),而在EBV阴性组中携带637G等位基因并不增加个体罹患鼻咽癌的风险,OR值为0.98(95%CI=0.59-1.66,P<0.001)。
结论1.TAP-1 637位点A/G基因多态性与云南汉族鼻咽癌遗传易感相关；2.TAP1基因多态性干扰HLA I抗原呈递在EBV感染致云南汉族鼻咽癌患病过程可能相关。
Objective To study the relationship between 637A/G gene polymorphisms of The transporter associated with antigen processing 1 gene and nasopharyngeal carcinomas(NPC),In order to find out the susceptible genes of nasopharyngeal carcinomas in Han population in Yunnan China.
Methods Two hundred thirty and three cases with NPC and Two hundred ninety and six cases matched cancer-free controls were genotyped for the TAP-1 637A/G polymorphism by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Epstein-Barr virus infection was detected by PCR。The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model.
Results Contrast with homozygous TAP1 637 AA, G allele significantly increasing risk of NPC was associated with homozygous 637 GG OR=4.26 (95% CI=2.08-8.66,P＜0.001) and heterozygous 637 AG OR=1.56 (95% CI=1.12-2.33; P= 0.036). The subjects at least having one TAP-1 637 G allele had OR of 1.88 (95% CI=1.35-2.82,P＜0.001). Furthermore, Smoking and EBV infection may increase the risk of developing NPC interacting with TAP1 637 A/G polymorphism.
Conclusions 1.The TAP1 637G allele is associated with the NPC in Han population in Yunnan China,2. EBV pathogenesis in NPC might be facilitated by polymorphisms in the TAP1 proteins.
引文
[1]贺智敏；陈主初；邵细云；何春梅；姚开泰等.中华病理学杂志1996.25(1)：17-20
[2]Weinstein IB,Carothers AM,Santella RM,etal.Molecular mechanism of multagenesis and multistage caieinogenesis.In:MandelsohnJ, Howley PM, MA Isral, etal.The molecular basis of cancer-OhiladelPhia:WB Saunders,1995,59-85.
[3]Castagna M.Phorbol esters as signal transducers and tumor Promoters.Biol Cell1987;59(1):3-13.
[4]Muir C,waterhouse J,Mack T.etal. IARC seientific publieation No.88.Lyon France:international ageney fir research on cancer,1987.
[5]游绍进；姚开泰；曹亚；胡维新等.中华肿瘤杂志1996.18(1)：23-26
[6]姚开泰；潘世成；黄季良等。湖南医学院学报1982；7：345
[7]陈孝光；姚开泰等.中国科学技术协会首届青年学术年会论文集医科分册。1992；45
[8]姚开泰：湖南医学院学报1982；7(1)：10-16
[9]Osato T, Imai S.Semin Cancer Biol 1996 Aug:7(4):175-82.
[10]Chan JK,Hui PK,TsangWY,et al.Caneer.1995Augl;76(3):413-22.
[11]Taner J,Weis J,Fearon D,Whang Y.etal.Cell1987Jul17:50(2):203-13.
[12]KaiserC, LauxqEickD, JochnerN, etal.Virol 1999May:73(5):4481-4.
[13]Adam JK, Odhav B, Bhoola KD. Immune responses in cancer. Pharmacol Ther. 2003 Jul;99(1):113-32.
[14]Hassen E, Farhat K, Gabbouj S, et al. TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian population. Cancer Genet Cytogenet.2007 May;175(1):41-6.
[15]Zheng Y, Shen H, Sturgis EM, et al.Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck:a case-control study. Carcinogenesis.2001 Aug;22(8):1195-1199.
[16]黄腾波,柳青,黄惠明,曹素梅.广东鼻咽癌遗传流行病学研究[J].中华医学遗传学杂志.2002,19(2)：134-137.
[17]曹素梅,郭翔,李宁炜,等.1142例住院广东籍鼻咽癌患者的临床资料分析[J].癌症,2006,25(2)：204-208.
[18]贾卫华,许宗利,冯炳健,等.广东鼻咽癌高危家族成员发病危险性的流行病学研究[J].癌症,2004,23(7)：767-770.
[19]Lee AW, Foo W, Mang O, et al. Changing epidemiology of nasopharyngeal carcinoma in Hong Kong over a 20-year period (1980-99):an encouraging reduction in both incidence and mortality [J]. Int J Cancer,2003,103(5):680-685.
[20]Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma [J]. Cancer Epidemiol Biomarkers,2006,15(10):1765-1777.
[21]周晓艺,刘荣华.148例老年鼻咽癌的放射治疗[J].肿瘤研究与临床,1997,9(1)：54-55.
[22]肖绍文,黄生富,陈文湛,等.50例老年鼻咽癌放射治疗体会[J].实用老年医学,1997,11 (2)：90.
[23]张少华,吕波,蔡悦成.肇庆市5352例鼻咽癌流行病学调查[J].中国基层医药,2005,12(7)：809-810.
[24]王兴榕,林春燕,李凡彩,等.高发及低发区鼻咽癌的病理组织学研究[J].中华病理学杂志,1993,22(3)：185-186.
[25]Burgos JS. Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma pathogenesis. Med Oncol,2005,22(2):113-121.
[26]Imashuku S. Clinical features and treatment strategies of Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis[J]. CritRev Oncol Hematol,2002,4H4(3):259-272.
[27]Koup RA. Virus escape from CTL recognition [J]. J Exp Med,1994,180:779.
[28]Campbell RD, Trowsdale J. Map of the human MHC. Immunol Today,1993,14:349-352.
[29]Lankat-Buttgereit B, Tampe R. The transporter associated with antigen processing:function and implications in human diseases. Physiol Rev,2002,82:187-204.
[30]Ritz U, Seliger B. The transporter associated with antigen processing (TAP):structural integrity, expression, function, and its clinical relevance. Mol Med,2001,7:149-158.
[31]Oancea G, O'Mara ML, Bennett WF, et al. Structural arrangement of the transmission interface in the antigen ABC transport complex TAP. Proc Natl Acad Sci U S A,2009, 106:5551-5556.
[32]Simone LC, Wang X, Solheim JC. A transmembrane tail:interaction of tapasin with TAP and the MHC class I molecule. Mol Immunol,2009,46:2147-2150. Epub 2009 Apr 9.
[33]Ofosu MH, Brown C, Cheatham W, et al. TAP1 polymorphism identified in African-American Graves' disease patients. Immunol Invest,1998,27:281-289.
[34]. Zhang SL, Chabod J, Penfornis A, et al. TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France. Eur J Immunogenet,2002,29:241-249.
[35]Song YW, Lee EB, Whang DH, et al. Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean patients. Hum Immunol,2005,66:810-817.
[36]Hassen E, Farhat K, Gabbouj S, et al. TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian population. Cancer Genet Cytogenet,2007,175:41-46.
[37]Kordi Tamandani DM, Sobti RC, Shekari M, et al. No association of TAP1 and TAP2 genes polymorphism with risk of cervical cancer in north Indian population. J Assist Reprod Genet, 2009,26:173-178. Epub 2009 Mar 5.
[38]Einstein MH, Leanza S, Chiu LG, et al. Genetic variants in TAP are associated with high-grade cervical neoplasia. Clin Cancer Res,2009,15:1019-1023.
[39]Deshpande A, Wheeler CM, Hunt WC, et al. Variation in HLA class Ⅰ antigen-processing genes and susceptibility to human papillomavirus type 16-associated cervical cancer. J Infect Dis,2008,197:371-381.
[40]金从国,王熙才,伍治平,等.1999-2002年云南省肿瘤医院恶性肿瘤住院病例分析.肿瘤防治杂志,2003,10(12)：1236-1238
[41]Ozyar E, Ayhan A, Korcum AF, et al. Prognostic role of Ebstein-Barr virus latent membrane protein-1 and interleukin-10 expression in patients with nasopharyngeal carcinoma. Cancer Invest,2004,22:483-491.
[42]Alves G, Macrini CM, De Souza Nascimento P, et al. Detection and expression of Epstein-Virus(EBV)DNA in tissues from penile tumours in Brazil. Cancer Lett,2004, 215:79-82.
[43]袁晖,杨蓓蓓,许则丰.鼻咽癌患者血.浆游离爱泼斯坦-巴尔病毒DNA定量测定的临床应用价值.中华耳鼻咽喉科杂志,2004,39：162-165.
[44]Salek-Ardakani S, Arrand JR, Mackett M. Epstein-Barr virus encoded interleukin-10 inhibits HLA-class Ⅰ, ICAM-1, and B7 expression on human monocytes:implications for immune evasion by EBV. Virology,2002,304:342-351.
[1]Spafford M F,Koch W M,Reed A L,.Et al.Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal cells by microsatellite analysis [J].Clin Cancer Res, 2001.7(3):607-612.
[2]Sanchez-Cespedes M,Esteller M,Wu L,et al.Gene promoter hypermethylation in tumors and serum of head and neck cancer patients [J].Cancer Res,2000,60(4):892-895.
[3]Rosas SL, Koch W, da Costa Carvalho MG,et al.Promoter hypermethylation patterns of p16, 06-methylguanine-DNA-methyltransferase, and death-associated portein kinase in tumors and saliva of head and neck cancer patients[J].Cancer Res,2001,61(3):939-942.
[4]Fliss MS,Usadel H,Caballero OL,et al.Faciled detection of mitochondrial DNA mutations in tumors and bodily fluids[J].Science,2000,287(5460):2017-2019.
[5]Srinivas PR, Kramer BS, Srivastava S. Trends in biomarker research for cancer detection. Lancet Oncol,2001,2(11):698-704.
[6]Simpson R J, Dorow DS. Cancer proteomics:from signaling networks to tumor markers.Trends Biotechnol,2001,19(10 suppl):40-48.
[7]赵实诚,许洋.蛋白质指纹技术在临床医学的应用与研究进展[J].中华检验医学杂志,2004,27(10)：706-709.
[8]Ciordia S, de Los Rios V, Albar JP. Contributions of advanced proteomics technologies to cancer diagnosis.Clin Transl Oncol,2006 Aug;8(8):566-80.
[9]Henderson N A,Steele R J.SELDI-TOF Proteomic analysis and cancer detection.Surgeon, 2005;3(6):383-390,422.
[10]CHO William Chi-Shin. Research Progress in SELDI-TOF-MS and its Clinical Applications. Chinese Journal of Biotechnolog,2006;Vol.22.No.6,871-876.
[11]Ho DW, Yang Z F, Wong BY, et al. Surface-enhanced laser desorption/ionization time-of-flightmass spectrometry serum protein profiling to identify nasopharyngeal carcinoma[J]. Cancer,2006,107(1):99-107.
[12]Wei YS, Zheng YH, Liang WB, et al. Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic analysis.Cancer.2008 Feb 1;112(3):544-51
[13]GuoX, Cao SM, Yu JK, et al. Distinct serumal proteomic patterns between ascending and descending types of loco-regionally advanced nasopharyngeal carcinoma assessed by surface enhanced laser desorption ionization and artificial neural network analyses[J]. Chin Med J(Engl),2005,18(22):1912-1917.
[14]Wang JX, Yu JK, Wang L, et al.Application of serum protein fingerprint in diagnosis of papillary thyroid carcinoma[J]. Proteomics,2006,6(19):5344-5349.
[15]卢秀波,王利,王家祥,等.血清蛋白质指纹图谱在甲状腺癌诊断中的应用.中华实验外科杂志,2006,vol23,NO.6,703-705
[16]张秀强,陈瑛,王巾帼,等.表面增强激光解吸离子化飞行时间质谱血清蛋白指纹图谱在喉癌诊断中的应用[J].临床耳鼻咽喉科杂志,2006,20(18)：842-846.
[17]XiaoX,ZhaoX,Liu J,et al.Discovery of laryngeal carcinoma by serum proteomic pattern analysis[J].Sci china C Life Sci,2004;47 (3) 210-223.
[18]曹素梅,郭翔,陈福进等.血清蛋白质谱结合人工神经网络在头颈部鳞癌诊断中的研究[J].癌症,2007,26(7)：767-770.
[19]Wadsworth JT,Somers KD,Cazares LH,et a.l Serum protein profiles to identify head and neck cancer[J]. Clin Cancer Res,2004,10(5):1625-1632.
[1]Li GY, Yao KT, Ronald G. Sister chromatid exchange and nasopharyngeal carcinoma [J]. Int J Cancer,1989,43(4):613-618.
[2]Mitelan F, Mark-Vendel, Mineur A, et al. A 3q+ marker chromosome in EBV-carring nasopharyngeal carcinomas[J]. Int J Cancer,1983,15(6):651-655.
[3]夏家辉, 卢惠霖.一条与人体鼻咽癌相关的标记染色体及其由来的初步探讨[J].遗传学报,1978,5(1)：19-21.
[4]邓龙文,姚开泰.人鼻咽癌上皮细胞株HNE1高分辨染色体显带分析[J].癌症,1993,12(4)：271-273.
[5]邓龙文,祝和成.人鼻咽癌上皮细胞株HNE2细胞遗传学研究[J].中华医学遗传学杂志,1993,10(1)：21-22.
[6]Lo K, Huang PW, Lee CK. Genetic changes in nasopharyngeal carcinoma[J]. Chin Med J, 1997,110(7):548-559.
[7]Wong N, Hui AB, Fan B, et al. Molecular cytogenetic characterization of nasopharyngeal carcinoma cell lines and xenografts by comparative genomic hybridization and spectral karyotyping[J]. Cancer Genet Cytogenet,2003,140(2):124-132.
[8]Latt SA, Schreck RR. In virto and in vivo analysis of sister chromatid exchange[J].Pharmacol Rev,1978,30(4):501-535.
[9]李桂源, 胡有秋, 潘世成,等.鼻咽癌患者姊妹染色单体互换频率变化及其影响因素的初步研究[J].湖南医学院学报,1983,8(3)：272-279.
[10]Kallioniemi A, Kallioniemi OP, Sudar D, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors[J]. Science,1992,258(5083):818-821.
[11]Chen YJ, Ko JY, Chen PJ, et al. Chromosomal aberrations in nasophayngeal carcinoma analysed by comparative genomic hybridization[J]. Genes Chromosomes & Cancer,1999, 25(2):169-175.
[12]Hui AB, Lo KW, Leung SF, et al. Detection of recurrentchromosomal gains and losses in primary nasopharyngeal carcinoma by comparative genomic hybridization[J]. Int J Cancer,1999, 82(4):498-503.
[13]Fan CS, Wong N, Leung SF, et al. Frequentc-myc and Int-2 over representations in nasopharyngeal carcinoma [J]. Hum Pathol,2000,31(2):169-178.
[14]Fang Y, Guan XY, Guo Y, et al. Analysis of genetic alterations in primary nasopharyngeal carcinoma by comparative genomic hybridization [J]. Gene Chromosomes Cancer, 2001,30(3):254-260.
[15]Chien G,Yuen PW,Kwong D, et al. Comparative genomic hybridization analysis of nasopharyngeal carcinoma:consistent patterns of genetic aberrations and clinicopathological correlations[J]. Cancer Genet Cytogenet,2001,126(1):63-67.
[16]李忠花,王璐,张小慧,等.比较基因组杂交研究鼻咽癌遗传变异[J].中华医学遗传学杂志,2001,18(5)：338-342.
[17]Mutirangura A,Tanunyuthawongese C, Pornthanakasem W, et al. Genomic alterations in nasopharyngeal carcinoma:loss of heterozygosity and Epstein-Barr virus infection [J]. Br J Cancer,1997,76(6):770-776.
[18]Shao JY, Wang HY, Huang XM, et al. Genome-wide allelotype analysis of sporadic primary nasopharyngeal carcinoma from southern China [J]. Int J Oncol,2000,17(6):1267-1275.
[19]Shao JY, Huang XM, Yu XJ, et al. Loss of heterozygosity and its correlation with clinical outcome and Epstein-Barr virus infection in nasopharyngeal carcinoma [J]. Anticancer Res,2001,21(4B):3021-3029.
[20]Lo KW, Teo PM, Hui AB, et al. High resolution allelotype of microdissected primary nasopharyngeal carcinoma [J]. Cancer Res,2000,60(13):3348-3353.
[21]李忠花,等.鼻咽癌基因组的杂合性丢失和微卫星不稳定性的研究[J].临床耳鼻喉科杂志,2001,15：70-75.
[22]Kwong J, LoK W, To KF, et al. Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma[J].Clin Cancer Res,2002,8(1):131-137.
[23]Lo KW, Huang DP. Genetic and pigenetic changes in nasopharyngeal carcinoma[J]. Semin Cancer Biol,2002,12(6):451-462.
[24]Ernberg I, Falk K, Minarovits J, et al. The role of methylation in the phenotype-dependent modulation of Epstein-Barr nuclear antigen 2 and latent membrane protein genes in cells latently infected with Epstein-Barr virus [J]. J Gen Virol,1989,70 (Pt 11): 2989-3002.
[25]Ambinder RF, Robertson KD, Tao Q. DNA methylation and the Epstein-Barr virus [J]. Semin Cancer Biol,1999,9(5):369-375.
[26]Tsai CN, Tsai CL, Tse KP, et al. The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases[J]. Proc Natl Acad Sci USA,2002,99(15):10084-10089.
[27]Chang HW, Chan A, Kwong DL, et al. Detection of hypermethylated RIZ1 gene in primary tumor, mouth, and throat rinsing fluid, nasopharyngeal swab, and peripheral blood of nasopharyngeal carcinoma patient [J]. Clin Cancer Res,2003,9(3):1033-1038.
[28]Hui AB, Lo KW, Kwong J, et al. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma [J]. Mol Carcino,2003,38(4):170-178.
[29]Kwong J, Lo KW, Chow LS, et al. Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma[J]. Int J Cancer,2005,113(3):386-392.
[30]Cheung HW, Ching YP, Nicholls JM, et al. Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation [J]. Mol Carcino,2005,43(4):237-245.
[31]Lung HL, Bangarusamy DK, Xie D, et al. THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma [J]. Oncogene,2005,24(43): 6525-6532.
[32]Lin YC, You L, Xu Z, et al. Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines [J]. Biochem Biophys Res Commun,2006,341(2):635-640.
[33]Horn PJ, Peterson CL. The bromodomain:a regulator of ATP-dependent chromatin remodeling [J]. Front Biosci,2001,6:D1019-1023.
[34]Cong Peng, Huaying Liu, Ming Zhou,et al.The transcriptional regulation role of BRD7 by binding to acetylated histone through bromodomain [J]. J Cell Biochem,2006,97(4):882-892.
[35]Chen ZY, Rex S, Tseng CC. Kruppel-like factor 4 is transactivated by butyrate in colon cancer cells [J]. J Nutr,2004,134(4):792-798.
[36]Feng BJ, Huang W, Shugart YY, et al. Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4 [J]. Nat Genet,2002,31(4):395-399.
[37]陈汉奎, 冯柄建,梁慧,等.单体型分析将家族性鼻咽癌易感基因定位于4p11~p14区域[J].科学通报,2003,48(16)：1776-1779.
[38]Chen CJ, Liang KY, Chang YS, et al. Multiple risk factors of nasopharyngeal carcinoma: Epstein-Barr virus, malarial infection, cigarette smoking and familial tendency [J]. Anticancer Res, 1990,10(2B):547-554.
[39]Lu CC, Chen JC, Jin YT, et al. Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese [J]. Int J Cancer,2003,103(6):745-751.
[40]Lu CC, Chen JC, Tsai ST, et al. Nasopharyngeal carcinoma-susceptibility locus is localized to a 132 kb segment containing HLA-A using high-resolution microsatellite mapping [J]. Int J Cancer,2005,115 (5):742-746.
[41]隋军,莫侨,李晓江,马静,任艳鑫,高伟,王涵,杨洁.TAP-1 637A/G基因多态性与中国云南汉族鼻咽癌易感性相关研究,中华耳鼻咽喉头颈外科杂志,2010,45(3) ：238-243.
[2]Weinstein IB,Carothers AM,Santella RM,etal.Molecular mechanism of multagenesis and multistage caieinogenesis.In:MandelsohnJ, Howley PM, MA Isral, etal.The molecular basis of cancer-OhiladelPhia:WB Saunders,1995,59-85.
[3]Castagna M.Phorbol esters as signal transducers and tumor Promoters.Biol Cell1987;59(1):3-13.
[4]Muir C,waterhouse J,Mack T.etal. IARC seientific publieation No.88.Lyon France:international ageney fir research on cancer,1987.
[5]游绍进；姚开泰；曹亚；胡维新等.中华肿瘤杂志1996.18(1)：23-26
[6]姚开泰；潘世成；黄季良等。湖南医学院学报1982；7：345
[7]陈孝光；姚开泰等.中国科学技术协会首届青年学术年会论文集医科分册。1992；45
[8]姚开泰：湖南医学院学报1982；7(1)：10-16
[9]Osato T, Imai S.Semin Cancer Biol 1996 Aug:7(4):175-82.
[10]Chan JK,Hui PK,TsangWY,et al.Caneer.1995Augl;76(3):413-22.
[11]Taner J,Weis J,Fearon D,Whang Y.etal.Cell1987Jul17:50(2):203-13.
[12]KaiserC, LauxqEickD, JochnerN, etal.Virol 1999May:73(5):4481-4.
[13]Adam JK, Odhav B, Bhoola KD. Immune responses in cancer. Pharmacol Ther. 2003 Jul;99(1):113-32.
[14]Hassen E, Farhat K, Gabbouj S, et al. TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian population. Cancer Genet Cytogenet.2007 May;175(1):41-6.
[15]Zheng Y, Shen H, Sturgis EM, et al.Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck:a case-control study. Carcinogenesis.2001 Aug;22(8):1195-1199.
[16]黄腾波,柳青,黄惠明,曹素梅.广东鼻咽癌遗传流行病学研究[J].中华医学遗传学杂志.2002,19(2)：134-137.
[17]曹素梅,郭翔,李宁炜,等.1142例住院广东籍鼻咽癌患者的临床资料分析[J].癌症,2006,25(2)：204-208.
[18]贾卫华,许宗利,冯炳健,等.广东鼻咽癌高危家族成员发病危险性的流行病学研究[J].癌症,2004,23(7)：767-770.
[19]Lee AW, Foo W, Mang O, et al. Changing epidemiology of nasopharyngeal carcinoma in Hong Kong over a 20-year period (1980-99):an encouraging reduction in both incidence and mortality [J]. Int J Cancer,2003,103(5):680-685.
[20]Chang ET, Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma [J]. Cancer Epidemiol Biomarkers,2006,15(10):1765-1777.
[21]周晓艺,刘荣华.148例老年鼻咽癌的放射治疗[J].肿瘤研究与临床,1997,9(1)：54-55.
[22]肖绍文,黄生富,陈文湛,等.50例老年鼻咽癌放射治疗体会[J].实用老年医学,1997,11 (2)：90.
[23]张少华,吕波,蔡悦成.肇庆市5352例鼻咽癌流行病学调查[J].中国基层医药,2005,12(7)：809-810.
[24]王兴榕,林春燕,李凡彩,等.高发及低发区鼻咽癌的病理组织学研究[J].中华病理学杂志,1993,22(3)：185-186.
[25]Burgos JS. Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma pathogenesis. Med Oncol,2005,22(2):113-121.
[26]Imashuku S. Clinical features and treatment strategies of Epstein-Barr Virus-associated hemophagocytic lymphohistiocytosis[J]. CritRev Oncol Hematol,2002,4H4(3):259-272.
[27]Koup RA. Virus escape from CTL recognition [J]. J Exp Med,1994,180:779.
[28]Campbell RD, Trowsdale J. Map of the human MHC. Immunol Today,1993,14:349-352.
[29]Lankat-Buttgereit B, Tampe R. The transporter associated with antigen processing:function and implications in human diseases. Physiol Rev,2002,82:187-204.
[30]Ritz U, Seliger B. The transporter associated with antigen processing (TAP):structural integrity, expression, function, and its clinical relevance. Mol Med,2001,7:149-158.
[31]Oancea G, O'Mara ML, Bennett WF, et al. Structural arrangement of the transmission interface in the antigen ABC transport complex TAP. Proc Natl Acad Sci U S A,2009, 106:5551-5556.
[32]Simone LC, Wang X, Solheim JC. A transmembrane tail:interaction of tapasin with TAP and the MHC class I molecule. Mol Immunol,2009,46:2147-2150. Epub 2009 Apr 9.
[33]Ofosu MH, Brown C, Cheatham W, et al. TAP1 polymorphism identified in African-American Graves' disease patients. Immunol Invest,1998,27:281-289.
[34]. Zhang SL, Chabod J, Penfornis A, et al. TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France. Eur J Immunogenet,2002,29:241-249.
[35]Song YW, Lee EB, Whang DH, et al. Association of TAP1 and TAP2 gene polymorphisms with systemic sclerosis in Korean patients. Hum Immunol,2005,66:810-817.
[36]Hassen E, Farhat K, Gabbouj S, et al. TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian population. Cancer Genet Cytogenet,2007,175:41-46.
[37]Kordi Tamandani DM, Sobti RC, Shekari M, et al. No association of TAP1 and TAP2 genes polymorphism with risk of cervical cancer in north Indian population. J Assist Reprod Genet, 2009,26:173-178. Epub 2009 Mar 5.
[38]Einstein MH, Leanza S, Chiu LG, et al. Genetic variants in TAP are associated with high-grade cervical neoplasia. Clin Cancer Res,2009,15:1019-1023.
[39]Deshpande A, Wheeler CM, Hunt WC, et al. Variation in HLA class Ⅰ antigen-processing genes and susceptibility to human papillomavirus type 16-associated cervical cancer. J Infect Dis,2008,197:371-381.
[40]金从国,王熙才,伍治平,等.1999-2002年云南省肿瘤医院恶性肿瘤住院病例分析.肿瘤防治杂志,2003,10(12)：1236-1238
[41]Ozyar E, Ayhan A, Korcum AF, et al. Prognostic role of Ebstein-Barr virus latent membrane protein-1 and interleukin-10 expression in patients with nasopharyngeal carcinoma. Cancer Invest,2004,22:483-491.
[42]Alves G, Macrini CM, De Souza Nascimento P, et al. Detection and expression of Epstein-Virus(EBV)DNA in tissues from penile tumours in Brazil. Cancer Lett,2004, 215:79-82.
[43]袁晖,杨蓓蓓,许则丰.鼻咽癌患者血.浆游离爱泼斯坦-巴尔病毒DNA定量测定的临床应用价值.中华耳鼻咽喉科杂志,2004,39：162-165.
[44]Salek-Ardakani S, Arrand JR, Mackett M. Epstein-Barr virus encoded interleukin-10 inhibits HLA-class Ⅰ, ICAM-1, and B7 expression on human monocytes:implications for immune evasion by EBV. Virology,2002,304:342-351.
[1]Spafford M F,Koch W M,Reed A L,.Et al.Detection of head and neck squamous cell carcinoma among exfoliated oral mucosal cells by microsatellite analysis [J].Clin Cancer Res, 2001.7(3):607-612.
[2]Sanchez-Cespedes M,Esteller M,Wu L,et al.Gene promoter hypermethylation in tumors and serum of head and neck cancer patients [J].Cancer Res,2000,60(4):892-895.
[3]Rosas SL, Koch W, da Costa Carvalho MG,et al.Promoter hypermethylation patterns of p16, 06-methylguanine-DNA-methyltransferase, and death-associated portein kinase in tumors and saliva of head and neck cancer patients[J].Cancer Res,2001,61(3):939-942.
[4]Fliss MS,Usadel H,Caballero OL,et al.Faciled detection of mitochondrial DNA mutations in tumors and bodily fluids[J].Science,2000,287(5460):2017-2019.
[5]Srinivas PR, Kramer BS, Srivastava S. Trends in biomarker research for cancer detection. Lancet Oncol,2001,2(11):698-704.
[6]Simpson R J, Dorow DS. Cancer proteomics:from signaling networks to tumor markers.Trends Biotechnol,2001,19(10 suppl):40-48.
[7]赵实诚,许洋.蛋白质指纹技术在临床医学的应用与研究进展[J].中华检验医学杂志,2004,27(10)：706-709.
[8]Ciordia S, de Los Rios V, Albar JP. Contributions of advanced proteomics technologies to cancer diagnosis.Clin Transl Oncol,2006 Aug;8(8):566-80.
[9]Henderson N A,Steele R J.SELDI-TOF Proteomic analysis and cancer detection.Surgeon, 2005;3(6):383-390,422.
[10]CHO William Chi-Shin. Research Progress in SELDI-TOF-MS and its Clinical Applications. Chinese Journal of Biotechnolog,2006;Vol.22.No.6,871-876.
[11]Ho DW, Yang Z F, Wong BY, et al. Surface-enhanced laser desorption/ionization time-of-flightmass spectrometry serum protein profiling to identify nasopharyngeal carcinoma[J]. Cancer,2006,107(1):99-107.
[12]Wei YS, Zheng YH, Liang WB, et al. Identification of serum biomarkers for nasopharyngeal carcinoma by proteomic analysis.Cancer.2008 Feb 1;112(3):544-51
[13]GuoX, Cao SM, Yu JK, et al. Distinct serumal proteomic patterns between ascending and descending types of loco-regionally advanced nasopharyngeal carcinoma assessed by surface enhanced laser desorption ionization and artificial neural network analyses[J]. Chin Med J(Engl),2005,18(22):1912-1917.
[14]Wang JX, Yu JK, Wang L, et al.Application of serum protein fingerprint in diagnosis of papillary thyroid carcinoma[J]. Proteomics,2006,6(19):5344-5349.
[15]卢秀波,王利,王家祥,等.血清蛋白质指纹图谱在甲状腺癌诊断中的应用.中华实验外科杂志,2006,vol23,NO.6,703-705
[16]张秀强,陈瑛,王巾帼,等.表面增强激光解吸离子化飞行时间质谱血清蛋白指纹图谱在喉癌诊断中的应用[J].临床耳鼻咽喉科杂志,2006,20(18)：842-846.
[17]XiaoX,ZhaoX,Liu J,et al.Discovery of laryngeal carcinoma by serum proteomic pattern analysis[J].Sci china C Life Sci,2004;47 (3) 210-223.
[18]曹素梅,郭翔,陈福进等.血清蛋白质谱结合人工神经网络在头颈部鳞癌诊断中的研究[J].癌症,2007,26(7)：767-770.
[19]Wadsworth JT,Somers KD,Cazares LH,et a.l Serum protein profiles to identify head and neck cancer[J]. Clin Cancer Res,2004,10(5):1625-1632.
[1]Li GY, Yao KT, Ronald G. Sister chromatid exchange and nasopharyngeal carcinoma [J]. Int J Cancer,1989,43(4):613-618.
[2]Mitelan F, Mark-Vendel, Mineur A, et al. A 3q+ marker chromosome in EBV-carring nasopharyngeal carcinomas[J]. Int J Cancer,1983,15(6):651-655.
[3]夏家辉, 卢惠霖.一条与人体鼻咽癌相关的标记染色体及其由来的初步探讨[J].遗传学报,1978,5(1)：19-21.
[4]邓龙文,姚开泰.人鼻咽癌上皮细胞株HNE1高分辨染色体显带分析[J].癌症,1993,12(4)：271-273.
[5]邓龙文,祝和成.人鼻咽癌上皮细胞株HNE2细胞遗传学研究[J].中华医学遗传学杂志,1993,10(1)：21-22.
[6]Lo K, Huang PW, Lee CK. Genetic changes in nasopharyngeal carcinoma[J]. Chin Med J, 1997,110(7):548-559.
[7]Wong N, Hui AB, Fan B, et al. Molecular cytogenetic characterization of nasopharyngeal carcinoma cell lines and xenografts by comparative genomic hybridization and spectral karyotyping[J]. Cancer Genet Cytogenet,2003,140(2):124-132.
[8]Latt SA, Schreck RR. In virto and in vivo analysis of sister chromatid exchange[J].Pharmacol Rev,1978,30(4):501-535.
[9]李桂源, 胡有秋, 潘世成,等.鼻咽癌患者姊妹染色单体互换频率变化及其影响因素的初步研究[J].湖南医学院学报,1983,8(3)：272-279.
[10]Kallioniemi A, Kallioniemi OP, Sudar D, et al. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors[J]. Science,1992,258(5083):818-821.
[11]Chen YJ, Ko JY, Chen PJ, et al. Chromosomal aberrations in nasophayngeal carcinoma analysed by comparative genomic hybridization[J]. Genes Chromosomes & Cancer,1999, 25(2):169-175.
[12]Hui AB, Lo KW, Leung SF, et al. Detection of recurrentchromosomal gains and losses in primary nasopharyngeal carcinoma by comparative genomic hybridization[J]. Int J Cancer,1999, 82(4):498-503.
[13]Fan CS, Wong N, Leung SF, et al. Frequentc-myc and Int-2 over representations in nasopharyngeal carcinoma [J]. Hum Pathol,2000,31(2):169-178.
[14]Fang Y, Guan XY, Guo Y, et al. Analysis of genetic alterations in primary nasopharyngeal carcinoma by comparative genomic hybridization [J]. Gene Chromosomes Cancer, 2001,30(3):254-260.
[15]Chien G,Yuen PW,Kwong D, et al. Comparative genomic hybridization analysis of nasopharyngeal carcinoma:consistent patterns of genetic aberrations and clinicopathological correlations[J]. Cancer Genet Cytogenet,2001,126(1):63-67.
[16]李忠花,王璐,张小慧,等.比较基因组杂交研究鼻咽癌遗传变异[J].中华医学遗传学杂志,2001,18(5)：338-342.
[17]Mutirangura A,Tanunyuthawongese C, Pornthanakasem W, et al. Genomic alterations in nasopharyngeal carcinoma:loss of heterozygosity and Epstein-Barr virus infection [J]. Br J Cancer,1997,76(6):770-776.
[18]Shao JY, Wang HY, Huang XM, et al. Genome-wide allelotype analysis of sporadic primary nasopharyngeal carcinoma from southern China [J]. Int J Oncol,2000,17(6):1267-1275.
[19]Shao JY, Huang XM, Yu XJ, et al. Loss of heterozygosity and its correlation with clinical outcome and Epstein-Barr virus infection in nasopharyngeal carcinoma [J]. Anticancer Res,2001,21(4B):3021-3029.
[20]Lo KW, Teo PM, Hui AB, et al. High resolution allelotype of microdissected primary nasopharyngeal carcinoma [J]. Cancer Res,2000,60(13):3348-3353.
[21]李忠花,等.鼻咽癌基因组的杂合性丢失和微卫星不稳定性的研究[J].临床耳鼻喉科杂志,2001,15：70-75.
[22]Kwong J, LoK W, To KF, et al. Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma[J].Clin Cancer Res,2002,8(1):131-137.
[23]Lo KW, Huang DP. Genetic and pigenetic changes in nasopharyngeal carcinoma[J]. Semin Cancer Biol,2002,12(6):451-462.
[24]Ernberg I, Falk K, Minarovits J, et al. The role of methylation in the phenotype-dependent modulation of Epstein-Barr nuclear antigen 2 and latent membrane protein genes in cells latently infected with Epstein-Barr virus [J]. J Gen Virol,1989,70 (Pt 11): 2989-3002.
[25]Ambinder RF, Robertson KD, Tao Q. DNA methylation and the Epstein-Barr virus [J]. Semin Cancer Biol,1999,9(5):369-375.
[26]Tsai CN, Tsai CL, Tse KP, et al. The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the downregulation of E-cadherin gene expression via activation of DNA methyltransferases[J]. Proc Natl Acad Sci USA,2002,99(15):10084-10089.
[27]Chang HW, Chan A, Kwong DL, et al. Detection of hypermethylated RIZ1 gene in primary tumor, mouth, and throat rinsing fluid, nasopharyngeal swab, and peripheral blood of nasopharyngeal carcinoma patient [J]. Clin Cancer Res,2003,9(3):1033-1038.
[28]Hui AB, Lo KW, Kwong J, et al. Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma [J]. Mol Carcino,2003,38(4):170-178.
[29]Kwong J, Lo KW, Chow LS, et al. Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma[J]. Int J Cancer,2005,113(3):386-392.
[30]Cheung HW, Ching YP, Nicholls JM, et al. Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation [J]. Mol Carcino,2005,43(4):237-245.
[31]Lung HL, Bangarusamy DK, Xie D, et al. THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma [J]. Oncogene,2005,24(43): 6525-6532.
[32]Lin YC, You L, Xu Z, et al. Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines [J]. Biochem Biophys Res Commun,2006,341(2):635-640.
[33]Horn PJ, Peterson CL. The bromodomain:a regulator of ATP-dependent chromatin remodeling [J]. Front Biosci,2001,6:D1019-1023.
[34]Cong Peng, Huaying Liu, Ming Zhou,et al.The transcriptional regulation role of BRD7 by binding to acetylated histone through bromodomain [J]. J Cell Biochem,2006,97(4):882-892.
[35]Chen ZY, Rex S, Tseng CC. Kruppel-like factor 4 is transactivated by butyrate in colon cancer cells [J]. J Nutr,2004,134(4):792-798.
[36]Feng BJ, Huang W, Shugart YY, et al. Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4 [J]. Nat Genet,2002,31(4):395-399.
[37]陈汉奎, 冯柄建,梁慧,等.单体型分析将家族性鼻咽癌易感基因定位于4p11~p14区域[J].科学通报,2003,48(16)：1776-1779.
[38]Chen CJ, Liang KY, Chang YS, et al. Multiple risk factors of nasopharyngeal carcinoma: Epstein-Barr virus, malarial infection, cigarette smoking and familial tendency [J]. Anticancer Res, 1990,10(2B):547-554.
[39]Lu CC, Chen JC, Jin YT, et al. Genetic susceptibility to nasopharyngeal carcinoma within the HLA-A locus in Taiwanese [J]. Int J Cancer,2003,103(6):745-751.
[40]Lu CC, Chen JC, Tsai ST, et al. Nasopharyngeal carcinoma-susceptibility locus is localized to a 132 kb segment containing HLA-A using high-resolution microsatellite mapping [J]. Int J Cancer,2005,115 (5):742-746.
[41]隋军,莫侨,李晓江,马静,任艳鑫,高伟,王涵,杨洁.TAP-1 637A/G基因多态性与中国云南汉族鼻咽癌易感性相关研究,中华耳鼻咽喉头颈外科杂志,2010,45(3) ：238-243.