非小细胞肺癌患者中肿瘤坏死因子相关凋亡诱导配体基因多态性及单倍型研究  

An analysis on gene polymorphisms and haplotypes of tumor necrosis factor-related apoptosis indu- cing ligand in the patients with non small-cell lung cancer

作　　者：吴江华[1] 王耀勇[2] 王桦[1] 叶旭军[1] 

机构地区：[1]武汉大学中南医院综合医疗科,430071 [2]山西医科大学附属汾阳医院

出　　处：《中华实验外科杂志》2013年第8期1585-1588,共4页Chinese Journal of Experimental Surgery

基　　金：湖北省卫生厅青年人才项目（QJX2010-19）

摘　　要：目的探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL）基因多态性及单倍型与非小细胞肺癌（NSCLC）的关系。方法收集NSCLC患者592例，健康对照者636例，聚合酶链反应（PCR）扩增TRAIL目的基因后，直接测序检测TRAIL基因3’非编码区（G1525A／G1588A／C1595T）3种单核苷酸多态性，并做TRAIL单倍型分析。结果与对照组比较，TRAILG1525A突变等位基因（A）和基因型（GA＋AA）的频率在NSCLC组中明显降低（P〈0．01）；NSCLC组TRAILG1588A和C1595T两位点突变等位基因（A）和（T）的频率亦明显低于对照组（P〈0．01）。进一步分层分析显示，Ⅰ期＋Ⅱ期NSCLC患者中TRAILC1595T突变等位基因（T）和（CT＋TT）基因型频率分别为47．89％和62．01％，Ⅲ期＋Ⅳ期NSCLC患者中分别为58．80％和74．65％，两组差异均有统计学意义[优势比（OR）值分别=1．553和1．804，95％可信区间（CI）：1．234～1．955和1．268．2．567，P〈0．01]。Ⅲ期＋Ⅳ期NSCLC患者中TRAILG1525A突变等位基因（A）的频率为47．54％，较Ⅰ期＋Ⅱ期NSCLC患者明显增加（40．75％，OR=1．318，95％CI：1．658～1．047，P〈0．05）。单倍型分析TRAIL基因（G1525A／G1588A／c1595T）3个位点紧密连锁，NSCLC组中AAT单倍型频率显著低于对照组（42．45％比58．23％，95％CI：1．525—2．824，P〈0．01）；GAT单倍型频率在NSCLC组中明显增高（9．98％比0．21％，95％CI：0．015—0．059，P〈0．01）。结论TRAIL（G1525A／G1588A／C1595T）基因多态性及单倍型与NSCLC的易感性密切相关。Objective To explore the associations between genetic polymorphisms and haplotypes of tumor necrosis factor-related apoptosis inducing ligand （TRAIL） and patients with non small-cell lung cancer （NSCLC）. Methods A total of 592 patients with NSCLC and 636 healthy controls were collected. After PCR amplification, TRAIL （G1525A/G1588A/C1595T） gene polymorphisms were detected by using direct sequencing. Haplotype analysis was also performed on all study subjects. Results Frequencies of variant allele （A） and genotype （GA ＋ AA） in TRAIL G1525A were significantly lower in NSCLC pa- tients than in healthy controls （ both P 〈 0. 01 ）. Frequencies of variant allele （A） and （T） in TRAIL G1588A and C1595T were also significantly lower in NSCLC patients than those in the healthy controls （both P 〈 0. 01 ）. In the further stratification analysis, frequencies of variant allele （T） and genotype （CT ＋TI＇） in TRAIL C1595T significantly differed between （stage I ＋ II ） and （stage III＋ IV） NSCLC patients [47.89% vs. 58.80% ,OR =2. 710, 95% confidence interval （CI） ： 1. 598-4. 596; 62. 01% vs. 74. 65% ,OR =2. 935, 95% CI： 1. 188-7. 249, respectively, both P 〈0. 05）. Moreover, frequency of va- riant allele （A） in TRAIL G1525A was significantly higher in （stage III＋ IV ） NSCLC patients than that in （stage I ＋ II ） NSCLC patients （47. 54% vs. 40. 75% ,OR = 1. 318, 95% CI： 1. 658-1. 047,P 〈0. 05）. In addition, TRAIL （G1525A/G1588A/C1595T） genes were found to be in a complete disequilibrium linkage in all study subjects. In contrast with healthy controls, frequency of AAT haplotype was significant- ly decreased （42.45% vs. 58. 23%, 95% CI： 1. 525-2. 824,P 〈0. 01 ）, wherease frequency of GAT hap- lotype was significantly increased in NSCLC patients （9.98% vs. 0. 21%, 95% CI： 0. 015-0. 059, P 〈 0. 01 ）. Conclusion Genetic polymorphisms and haplotypes of TRAIL （G1525A/G1588A/C1595T） genesmay be significantly correlat

关 键 词：非小细胞肺癌 肿瘤坏死因子 基因多态性 

分 类 号：R734.2[医药卫生—肿瘤]