Timirci-Kahraman Ozlem, Ozkan Nazli Ezgi, Turan Saime, Farooqi Ammad Ahmad, Verim Levent, Ozturk Tulin, Inal-Gultekin Guldal, Isbir Turgay, Ozturk Oguz, Yaylim Ilhan
1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
2 Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital , Islamabad, Pakistan .
Genet Test Mol Biomarkers. 2015 Jun;19(6):309-15. doi: 10.1089/gtmb.2015.0050. Epub 2015 May 8.
The aim of this study was to evaluate the role of polymorphisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes in bladder cancer susceptibility in a Turkish population.
The study group included 91 bladder cancer patients, while the control group comprised 139 individuals with no evidence of malignancy. Gene polymorphisms of TRAIL C1595T (rs1131580) and DR4 C626G (rs4871857) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
The frequency of the TRAIL 1595 TT genotype was significantly lower in patients with bladder cancer compared to controls (p<0.001; odds ratios [OR]=0.143; 95% confidence interval [CI]=0.045-0.454). A significantly increased risk for developing bladder cancer was found for the group bearing a C allele for TRAIL C1595T polymorphism (p<0.001; OR=1.256; 95% CI=1.138-1.386). The observed genotype and allele frequencies of DR4 626 C/G in all groups were in agreement with the Hardy-Weinberg equilibrium (p=0.540). However, the frequency of DR4 GG genotype was found to be 2.1-fold increased in the bladder cancer patients with high-grade tumor, when compared to those having low-grade tumor (p=0.036). Additionally, combined genotype analysis showed that the frequency of TRAILCT-DR4GG was significantly higher in patients with bladder cancer in comparison with those of controls (p=0.037; OR=2.240; 95% CI=1.138-1.386).
Our study provides new evidence that TRAIL 1595 C allele may be used as a low-penetrant risk factor for bladder cancer development in a Turkish population. Otherwise, gene-gene interaction analysis revealed that the DR4GG genotype may have a predominant effect on the increased risk of bladder cancer over the TRAIL CT genotype.
本研究旨在评估肿瘤坏死因子相关凋亡诱导配体（TRAIL）和死亡受体（DR4）基因多态性在土耳其人群膀胱癌易感性中的作用。
研究组包括91例膀胱癌患者，对照组由139例无恶性肿瘤证据的个体组成。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对TRAIL C1595T（rs1131580）和DR4 C626G（rs4871857）基因多态性进行基因分型。
与对照组相比，膀胱癌患者中TRAIL 1595 TT基因型的频率显著降低（p<0.001；比值比[OR]=0.143；95%置信区间[CI]=0.045-0.454）。发现携带TRAIL C1595T多态性C等位基因的组患膀胱癌的风险显著增加（p<0.001；OR=1.256；95% CI=1.138-1.386）。所有组中DR4 626 C/G的观察基因型和等位基因频率均符合哈迪-温伯格平衡（p=0.540）。然而，与低级别肿瘤患者相比，高级别肿瘤膀胱癌患者中DR4 GG基因型的频率增加了2.1倍（p=0.036）。此外，联合基因型分析表明，与对照组相比，膀胱癌患者中TRAILCT-DR4GG的频率显著更高（p=0.037；OR=2.240；95% CI=1.138-1.386）。
我们的研究提供了新的证据，表明TRAIL 1595 C等位基因可能作为土耳其人群膀胱癌发生的低外显率危险因素。否则，基因-基因相互作用分析显示，DR4GG基因型可能比TRAIL CT基因型对膀胱癌风险增加具有主要影响。
