Sarwar R, Mansoor Q, Farooqi A A, Shahzad S, Fayyaz S, Ismail M
Institute of Biomedical and Genetic Engineering (IBGE) Islamabad Pakistan.
Institute of Biomedical and Genetic Engineering (IBGE) Islamabad Pakistan
Cell Mol Biol (Noisy-le-grand). 2015 Dec 19;61(8):53-6.
TRAIL mediated signaling in cancer cells has emerged as one amongst the most deeply studied molecular phenomenon. Recent breakthroughs have shown that overexpression of anti-apoptotic proteins, inactivation of pro-apoptotic proteins, transcriptional downregulation of TRAIL, DR4/DR5, degradation of DR/DR5 are some of the mechanisms which dramatically abrogate TRAIL induced apoptosis in cancer cells. Data obtained through genetic studies has highlighted highly polymorphic nature of DR4 and in accordance with this concept, we investigated the association between Head and Neck Cancer and polymorphisms in TRAIL (1595 C/T) and DR4 (C626G and A1322G) gene. We selected 100 patients with Head and Neck Cancer and 100 healthy, sex and age matched volunteers randomly. C626G and A1322G in DR4 gene were analyzed using Polymerase Change Reaction (PCR) - Restriction Fragment Length Polymorphism (RFLP) and Amplification Refractory Mutation System (ARMS) techniques respectively. For TRAIL gene 1595 C>T genotypes, there was no statistically significant role of homozygous CC or TT in Head and Neck cancer. CC was 58% in patients and 49% in controls. CT was 30% in patients and 43% in controls. TT was 12% in patients and 8% in controls. Allele frequency for C was noted to be 0.73 (patients) and 0.705 (controls), p-value (1). For T, 0.025 (patients) and 0.001(controls), p-value (0.88). The genotyping for DR4 gene 626 C>G polymorphism was done for 100 head and neck cancer patients and 100 age and sex matched healthy controls. All the genotypes for the polymorphism were in Hardy-Weinberg Equilibrium. For DR4626 C>G genotype, CC was 10% in patients and 2% in controls. GC was 63% in patients and 40% in controls. GG was 27% in patients and 58% in controls. Interestingly, in DR4 genotyping, CC was predisposing factor and GG acted as a protective factor. Allele frequency for C was noted to be 0.41 (patients) and 0.22 (controls), p-value (0.81). For G, 0.585 (patients) and 0.78 (controls), p-value (0.867). For the A1322G polymorphism, TT was 23% in patients and 36% in controls with a p-value 0.09 (table 6). CT was statistically significant in patients (45%) and controls (28%), p-value 0.04. CC was non-significant in patients (32%) and controls (36%), p-value 0.62 (table 6). C allele was 0.45% in patients and 0.5% in controls. T allele was 0.54% in patients and 0.5% in controls. Future studies must converge on somatic mutations, epigenetic mutations and expression analysis of TRAIL and DR4 to get a step closer to individualized medicine.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）介导的癌细胞信号传导已成为研究最深入的分子现象之一。最近的突破表明，抗凋亡蛋白的过表达、促凋亡蛋白的失活、TRAIL、死亡受体4（DR4）/死亡受体5（DR5）的转录下调、DR4/DR5的降解是癌细胞中显著消除TRAIL诱导的细胞凋亡的一些机制。通过基因研究获得的数据突出了DR4的高度多态性，根据这一概念，我们研究了头颈癌与TRAIL基因（1595 C/T）和DR4基因（C626G和A1322G）多态性之间的关联。我们随机选择了100名头颈癌患者和100名年龄、性别匹配的健康志愿者。分别使用聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）技术和扩增阻滞突变系统（ARMS）技术分析DR4基因中的C626G和A1322G。对于TRAIL基因1595 C>T基因型，纯合子CC或TT在头颈癌中没有统计学上的显著作用。患者中CC为58%，对照组中为49%。患者中CT为30%，对照组中为43%。患者中TT为12%，对照组中为8%。C的等位基因频率在患者中为0.73，在对照组中为0.705，p值（1）。对于T，患者中为0.025，对照组中为0.001，p值（0.88）。对100名头颈癌患者和100名年龄、性别匹配的健康对照进行了DR4基因626 C>G多态性的基因分型。该多态性的所有基因型均处于哈迪-温伯格平衡。对于DR4 626 C>G基因型，患者中CC为10%，对照组中为2%。患者中GC为63%，对照组中为40%。患者中GG为27%，对照组中为58%。有趣的是，在DR4基因分型中，CC是一个易感因素，GG起到保护作用。C的等位基因频率在患者中为0.41，在对照组中为0.22，p值（0.81）。对于G，患者中为0.585，对照组中为0.78，p值（0.867）。对于A1322G多态性，患者中TT为23%，对照组中为36%，p值为0.09（表6）。患者中CT（45%）和对照组中CT（28%）具有统计学意义，p值为0.04。患者中CC（32%）和对照组中CC（36%）无统计学意义，p值为0.62（表6）。患者中C等位基因为0.45%，对照组中为0.5%。患者中T等位基因为0.54%，对照组中为0.5%。未来的研究必须集中在TRAIL和DR4的体细胞突变、表观遗传突变和表达分析上，以便更接近个性化医疗。
