肿瘤坏死因子相关凋亡诱导配体基因多态性与非小细胞肺癌相关性分析

Association Between Gene Polymorphisms of Tumor Necrosis Factor-Related Apoptosis Inducing Ligand and Non Small-Cell Lung Cancer

目的:探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因多态性与非小细胞肺癌(NSCLC)的关系。方法:收集NSCLC患者592例,健康对照者636名,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。结果:与对照组相比较,TRAIL G1525A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均<0.01);NSCLC组TRAIL G1588A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均<0.01)。进一步分层分析发现,Ⅰ期+Ⅱ期NSCLC患者中TRAIL C1595T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%,两组比较差异均有统计学意义(OR分别=1.553和1.804,95%CI:1.234-1.955和1.268-2.567,P均<0.001)。Ⅲ期+Ⅳ期NSCLC患者中TRAIL G1525A突变等位基因(A)的频率为47.54%,较Ⅰ期+Ⅱ期NSCLC患者(40.75%)明显增加(OR=1.318,95%CI:1.658-1.047,P=0.019)。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 of tumor necrosis factor-related apoptosis inducing ligand （TRAIL） and 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 direct sequencing. Results： Compared with that respectively in controls, frequencies of variant allele （A） and genotype （GA＋AA） in TRAIL G1525A were significantly lower in NSCLC patients （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 controls （both P〈0.01）. In the further stratification analysis, frequencies of variant allele （T） and genotype （CT＋TT） in TRAIL C1595T significantly differed between stage （ I ＋ II ） and stage （Ⅲ ＋ IV ） NSCLC patients （47.89% vs 58.80%, OR=2.710, 95%CI： 1.598-4.596; 62.01% vs 74.65%, OR=2.935,95%CI. 1.188-7.249, respectively, both P〈O.05）. Moreover, frequency of variant 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= O.019）. In addition, TRAIL （G1525A/G1588A/C1595T） genes were found to be in a complete disequilibrium linkage in all study subjects. Conclusion： Genetic polymorphisms of TRAIL （G1525A/ G1588A/C1595T） genes may be significantly correlated with the susceptibility to NSCLC in Chinese patients.