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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 investigate the relationship between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene polymorphism and non-small cell lung cancer (NSCLC). Methods: 592 NSCLC patients and 636 healthy controls were collected. After TRAIL gene was amplified by PCR, the three single nucleotide polymorphisms of TRAIL gene 3 ’untranslated region (G1525A / G1588A / C1595T) were detected by direct sequencing. Results: Compared with the control group, the frequency of allele (A) and genotype (GA + AA) of TRAIL G1525A was significantly decreased in NSCLC group (all P <0.01). The mutations of TRAIL G1588A and C1595T The frequencies of alleles (A) and (T) were also significantly lower than those of the control group (all P <0.01). Further stratified analysis showed that the frequencies of TRAIL C1595T mutation allele (T) and (CT + TT) genotypes were 47.89% and 62.01% in stage Ⅰ + Ⅱ NSCLC patients respectively. The frequencies of TRAIL C1595T mutation in stage Ⅲ + Ⅳ NSCLC patients were 58.80% and 74.65%, respectively. There were significant differences between the two groups (OR = 1.553 and 1.804, 95% CI: 1.234-1.955 and 1.268-2.567 respectively, P <0.001). The frequency of TRAIL G1525A mutation allele (A) in stage Ⅲ + Ⅳ NSCLC patients was 47.54%, which was significantly higher than that in stage Ⅰ + stage NSCLC patients (40.75%) (OR = 1.318,95% CI: 1.658-1.047, P = 0.019). Conclusion: The polymorphisms and haplotypes of TRAIL (G1525A / G1588A / C1595T) are closely related to the susceptibility to NSCLC.