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NFKB1 和 NFKBIA 基因多态性对肝细胞癌易感性及临床病理特征的影响。

Effects of NFKB1 and NFKBIA gene polymorphisms on hepatocellular carcinoma susceptibility and clinicopathological features.

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

出版信息

PLoS One. 2013;8(2):e56130. doi: 10.1371/journal.pone.0056130. Epub 2013 Feb 14.

Abstract

BACKGROUND

Constitutive activation of nuclear factor (NF)-κB is frequently observed in hepatocellular carcinoma (HCC). The current study examined associations of polymorphisms within promoter regions of NFKB1 encoding NF-κB1 and NFKBIA encoding IκBα with the susceptibility of developing HCC and clinicopathological characteristics of the tumors.

METHODOLOGY AND PRINCIPAL FINDINGS

Genetic polymorphisms of NFKB1 and NFKBIA were analyzed by a real-time polymerase chain reaction (PCR) in 135 HCC patients and 520 healthy controls. The genotypic frequency of the NFKB1 -94 Ins polymorphism in HCC patients was significantly higher than that of the controls (adjusted odds ratio (AOR) = 2.23; 95% confidence interval (CI) 1.32∼3.77). No statistical significance was observed for the distribution frequency of the NFKBIA --519 C/T, -826 C/T, or -881 A/G genotype and haplotype polymorphisms between HCC patients and controls. Furthermore, female HCC patients carrying the NFKB1 -94 Ins polymorphism were associated with lower clinical stages and smaller tumor sizes.

CONCLUSIONS

Our results indicate that the NFKB1 -94 Ins promoter polymorphism increased the risk of HCC, and may be applied as a predictive factor for the clinical stage and tumor size in female HCC patients.

摘要

背景

核因子 (NF)-κB 的组成性激活在肝细胞癌 (HCC) 中经常观察到。本研究检查了 NFKB1 编码 NF-κB1 和 NFKBIA 编码 IκBα 的启动子区域内的多态性与 HCC 易感性以及肿瘤的临床病理特征之间的关联。

方法和主要发现

通过实时聚合酶链反应 (PCR) 在 135 名 HCC 患者和 520 名健康对照中分析了 NFKB1 和 NFKBIA 的遗传多态性。HCC 患者中 NFKB1-94Ins 多态性的基因型频率明显高于对照组(调整后的优势比 (AOR)=2.23;95%置信区间 (CI) 1.32∼3.77)。在 HCC 患者和对照组之间,NFKBIA--519C/T、-826C/T 或 -881A/G 基因型和单倍型多态性的分布频率没有统计学意义。此外,携带 NFKB1-94Ins 多态性的女性 HCC 患者与较低的临床分期和较小的肿瘤大小相关。

结论

我们的结果表明,NFKB1-94Ins 启动子多态性增加了 HCC 的风险,并且可以作为女性 HCC 患者临床分期和肿瘤大小的预测因子。

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