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肿瘤坏死因子相关凋亡诱导配体(TRAIL)和死亡受体(DR4)基因中的遗传变异导致巴基斯坦人群患结直肠癌的易感性增加。

Genetic variants in the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes contribute to susceptibility to colorectal cancer in pakistani population.

作者信息

Zahoor A, Mansoor Q, Farooqi A A, Fayyaz S, Naz G, Ismail M

机构信息

Institute of Biomedical and Genetic Engineering (IBGE) Islamabad Pakistan.

Institute of Biomedical and Genetic Engineering (IBGE) Islamabad Pakistan ammadahmad638@yahoo.com.

出版信息

Cell Mol Biol (Noisy-le-grand). 2015 Oct 30;61(6):108-12.

PMID:26518902
Abstract

TRAIL mediated signaling in cancer cells has emerged as one amongst the most deeply studied molecular phenomenon. Data obtained through genetic studies has highlighted highly polymorphic nature of DR4 and in accordance with this concept, we aimed to investigate the association between Colorectal cancer and polymorphisms in TRAIL and DR4 gene. We selected 100 patients with colorectal 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. PCR-RFLP was used to study TRAIL 1595 C>T. TRAIL gene 1595 C>T genotypes percentage in colorectal cancer patients was statistically non-significant. CC was 43% in patients and 50% in controls. CT was 45% in patients and 43% in controls. TT was 12% in patients and 7% in controls. C allele was 0.655% in cancer patients and 0.715% in controls. T allele was 0.345% in patients and 0.285% in controls. DR4 gene 626 C>G genotypes percentage analysis indicated that CC was 28% in patients and 2% in controls. GC was 42% in patients and 40% in controls. GG was 30% in patients and 58% in controls. CC was statistically significant (p=0.00000207) in cancer patients. C allele was 0.49% in patients and 0.22% in controls. G allele was 0.51% in patients and 0.78% in controls. For DR4 A1322G, homozygous GG genotype was 36% in the patients and in controls. There was statistically insignificant difference (p> 0.05). The heterozygous GT genotype was 30% in patients and 29% in controls. This difference was statistically insignificant (p value > 0.05). Similarly, the homozygous genotype TT of the minor allele was (35%) in controls and patients (34 %). This difference was also statistically insignificant (p value > 0.05). C allele was 0.51% in patients and 0.5% in controls. T allele was 0.49% in patients and 0.495% in controls. Future studies must converge on a larger sample size, sporadic mutations of DR4 and TRAIL and expression profiling.

摘要

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。通过基因研究获得的数据突出了死亡受体4(DR4)的高度多态性,基于这一概念,我们旨在研究结直肠癌与TRAIL和DR4基因多态性之间的关联。我们随机选择了100例结直肠癌患者和100名年龄和性别匹配的健康志愿者。使用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)和扩增阻滞突变系统(ARMS)技术分析DR4基因中的C626G和A1322G。PCR-RFLP用于研究TRAIL 1595 C>T。结直肠癌患者中TRAIL基因1595 C>T基因型百分比在统计学上无显著差异。患者中CC基因型占43%,对照组中占50%。患者中CT基因型占45%,对照组中占43%。患者中TT基因型占12%,对照组中占7%。癌症患者中C等位基因占0.655%,对照组中占0.715%。患者中T等位基因占0.345%,对照组中占0.285%。DR4基因626 C>G基因型百分比分析表明,患者中CC基因型占28%,对照组中占2%。患者中GC基因型占42%,对照组中占40%。患者中GG基因型占30%,对照组中占58%。癌症患者中CC基因型具有统计学显著性(p=0.00000207)。患者中C等位基因占0.49%,对照组中占0.22%。患者中G等位基因占0.51%,对照组中占0.78%。对于DR4 A1322G,患者和对照组中纯合GG基因型均为36%。差异无统计学意义(p>0.0

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