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

Abstract

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/CI595T) 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 patients 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 + 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％ 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 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 ＜ 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 significantly decreased (42.45％ vs.58.23％,95％ CI:1.525-2.824,P ＜0.01),wherease frequency of GAT haplotype 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) genes may be significantly correlated with the susceptibility to NSCLC in Chinese patients. Key words: Non small-cell lung cancer; Tumor necrosis factor; Gene polymorphism