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在土耳其人群中,NAD(P)H:醌氧化还原酶1(NQO1)C609T基因多态性与肝细胞癌发生风险无关联。

No association of NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and risk of hepatocellular carcinoma development in Turkish subjects.

作者信息

Akkiz Hikmet, Bayram Süleyman, Bekar Aynur, Akgöllü Ersin, Ülger Yakup, Kaya Berrin Yalinbaş, Sandikçi Macit, Özdil Burhan

机构信息

Department of Gastroenterology, Faculty of Medicine, Cukurova University, Adana, Turkey.

出版信息

Asian Pac J Cancer Prev. 2010;11(4):1051-8.

Abstract

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of numerous quinoid compounds into their less toxic form, thus NQO1 protecting cells against oxidative stress. The gene coding for NQO1 has a single nucleotide polymorphism (C-->T) at nucleotide position 609 (proline to serine substitution at position 187 in amino acid sequence (P187S)) (rs1800566) of the NQO1 cDNA which results in very low enzimatic activity, so it would be expected that individuals with the homologous NQO1 C609T polymorphism would have a susceptibility developing cancer. Previous studies of the association between functional NQO1 C609T polymorphism and several human cancers have had mixed findings but association of NQO1 C609T polymorphism with hepatocellular carcinoma (HCC) development has yet to be investigated. In this study, we aim to evaluate the the association of NQO1 C609T with the risk of hepatocellular carcinoma (HCC) development among Turkish population. NQO1 C609T polymorphism was investigated in 167 confirmed subjects with HCC and 167 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. There is no association between the allel or genotype of NQO1 C609T polymorphism and HCC development risk in the Turkish subjects examined (p>0.05). Our result demonstrate for the first time that the NQO1 C609T polymorphism is not a genetic susceptibility factor for HCC in the Turkish population. Independent studies are need to validate our findings in a larger series, as well as in patients of different ethnic origins.

摘要

NAD(P)H:醌氧化还原酶1(NQO1)是一种胞质酶,可催化多种醌类化合物的双电子还原反应,使其转化为毒性较低的形式,从而保护细胞免受氧化应激的影响。编码NQO1的基因在NQO1 cDNA的核苷酸位置609处存在单核苷酸多态性(C→T)(氨基酸序列中第187位脯氨酸被丝氨酸取代(P187S))(rs1800566),这导致酶活性非常低,因此预计具有同源NQO1 C609T多态性的个体患癌症的易感性会增加。先前关于功能性NQO1 C609T多态性与几种人类癌症之间关联的研究结果不一,但NQO1 C609T多态性与肝细胞癌(HCC)发生之间的关联尚未得到研究。在本研究中,我们旨在评估土耳其人群中NQO1 C609T与肝细胞癌(HCC)发生风险之间的关联。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析,对167例确诊的HCC患者和167例年龄、性别、吸烟和饮酒情况相匹配的无癌对照受试者进行了NQO1 C609T多态性研究。在所检测的土耳其受试者中,NQO1 C609T多态性的等位基因或基因型与HCC发生风险之间无关联(p>0.05)。我们的结果首次表明,NQO1 C609T多态性不是土耳其人群中HCC的遗传易感性因素。需要进行独立研究,以在更大的样本系列以及不同种族来源的患者中验证我们的发现。

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