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NQO1基因C609T多态性与肝细胞癌风险

The NQO1 C609T polymorphism and hepatocellular carcinoma risk.

作者信息

Fan Yonggang, Hu Dingwen, Feng Bing, Wang Wei

机构信息

Department of General Surgery, The First Affiliated Hospital of Henan Science and Technology University, Luoyang, 471000, Henan Province, China,

出版信息

Tumour Biol. 2014 Aug;35(8):7343-50. doi: 10.1007/s13277-014-1712-8. Epub 2014 Feb 16.

Abstract

NAD(P)H quinine oxidoreductase 1 (NQO1) enzyme plays a crucial role in the protection against oxidative stress. The polymorphism of NQO1 C609T has been implicated in the development of hepatocellular carcinoma (HCC). However, the findings were inconsistent due to different ethnicity, sample size, and source of controls in individual studies. To better estimate the association of NQO1 C609T polymorphism with HCC risk, we performed a meta-analysis of all currently available studies on the susceptibility to HCC. The meta-analysis included three independent studies with a total of 1, 595 subjects. The association was assessed under five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of HCC (ORT vs. C = 1.47, 95 % CI 1.07-2.00, P OR = 0.016; ORTT vs. CC = 2.06, 95 % CI 1.06-3.98, P OR = 0.032; ORTC vs. CC = 1.33, 95 % CI 1.06-1.67, P OR = 0.012; ORTT + TC vs. CC = 1.46, 95 % CI 1.19-1.81, P OR < 0.001; ORTT vs. CC + TC = 1.62, 95 % CI 1.25-2.09, P OR < 0.001). Stratified analyses in Asians and hospital-based case-control studies further demonstrated the significant correlation. Sensitivity analysis confirmed the reliability of these findings. Our study firstly shows that individuals carrying the NQO1 C609T variant allele and genotypes are more susceptible to HCC, particularly for Asians.

摘要

烟酰胺腺嘌呤二核苷酸磷酸(NAD(P)H)醌氧化还原酶1(NQO1)在抵御氧化应激中起关键作用。NQO1基因C609T多态性与肝细胞癌(HCC)的发生有关。然而,由于个体研究中种族、样本量和对照来源不同,研究结果并不一致。为了更好地评估NQO1基因C609T多态性与HCC风险的关联,我们对目前所有关于HCC易感性的研究进行了荟萃分析。该荟萃分析纳入了三项独立研究,共1595名受试者。在五种不同的基因模型下评估了这种关联。总体分析表明,变异等位基因和基因型与HCC风险增加显著相关(T等位基因与C等位基因相比:优势比(OR)=1.47,95%置信区间(CI)为1.07 - 2.00,P值=0.016;TT基因型与CC基因型相比:OR = 2.06,95%CI为1.06 - 3.98,P值=0.032;TC基因型与CC基因型相比:OR = 1.33,95%CI为1.06 - 1.67,P值=0.012;TT + TC基因型与CC基因型相比:OR = 1.46,95%CI为1.19 - 1.81,P值<0.001;TT基因型与CC + TC基因型相比:OR = 1.62,95%CI为1.25 - 2.09,P值<0.001)。在亚洲人群以及基于医院的病例对照研究中的分层分析进一步证实了这种显著相关性。敏感性分析证实了这些发现的可靠性。我们的研究首次表明,携带NQO1基因C609T变异等位基因和基因型的个体更易患HCC,尤其是亚洲人。

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