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埃及患者中FasL基因-844T/C多态性与肝细胞癌风险之间的显著关联。

Significant association between FasL gene -844T/C polymorphism and risk to hepatocellular carcinoma in Egyptian patients.

作者信息

Khalifa Rania H, Bahgat Dina M Rasheed, Darwish Hatem Abdel Hamid, Shahin Rasha Mohamad Hosny

机构信息

Department of Clinical & Chemical Pathology, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt.

Department of Clinical & Chemical Pathology, Kasr Al-Ainy, School of Medicine, Cairo University, Egypt.

出版信息

Immunol Lett. 2016 Apr;172:84-8. doi: 10.1016/j.imlet.2016.02.007. Epub 2016 Feb 15.

Abstract

Fas/Fas ligand (FasL) system is the most critical apoptotic signaling entity in the extrinsic apoptotic pathway; hence mutations affecting this pathway may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between the FasL -844T/C polymorphism and the risk of hepatocellular carcinoma (HCC) in a cohort of Egyptian patients and explored the relationship of various clinical and pathological parameters with this single nucleotide polymorphism (SNP). Blood samples were withdrawn from hundred HCC patients and 100 age-, sex- and ethnically matched controls. The FasL -844T/C (rs763110) gene polymorphism was typed from genomic DNA using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Genotype distributions and allelic frequencies between patients and control subjects showed that the TT homozygous patients were two times more likely to develop HCC (p=0.011). Also, the T allele was found to be a significant risk factor for the disease (OR 1.970, 95% CI 1.250-3.105, p=0.003). No association was detected between different parameters of the disease and the SNP. For the first time, our results suggest that the -844T/C polymorphism in the FasL gene confers risk to HCC. The alarming increase in the incidence of HCC in Egypt encourages further studies to document our results in a larger sample, and recommends more genetic studies hoping to define a genomic risk prediction specific to this cancer in our population.

摘要

Fas/Fas配体(FasL)系统是外源性凋亡途径中最关键的凋亡信号传导实体;因此,影响该途径的突变可能会阻止免疫系统清除新形成的肿瘤细胞,从而导致肿瘤形成。本研究调查了埃及患者队列中FasL -844T/C多态性与肝细胞癌(HCC)风险之间的关联,并探讨了各种临床和病理参数与这种单核苷酸多态性(SNP)的关系。从100例HCC患者以及100例年龄、性别和种族匹配的对照者中采集血样。使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析从基因组DNA中检测FasL -844T/C(rs763110)基因多态性。患者和对照者之间的基因型分布和等位基因频率显示,TT纯合患者发生HCC的可能性是对照组的两倍(p = 0.011)。此外,发现T等位基因是该疾病的一个重要危险因素(OR 1.970,95% CI 1.250 - 3.105,p = 0.003)。未检测到该疾病的不同参数与SNP之间存在关联。我们的结果首次表明,FasL基因中的 -844T/C多态性会增加患HCC的风险。埃及HCC发病率惊人的上升促使进一步研究以在更大样本中证实我们的结果,并建议开展更多基因研究,希望能确定针对我国人群中这种癌症的基因组风险预测。

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