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缺氧诱导因子 1-α 基因多态性与结直肠癌预后的关系。

Association of hypoxia-inducible factor 1-alpha gene polymorphisms and colorectal cancer prognosis.

机构信息

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.

出版信息

Anticancer Res. 2010 Jun;30(6):2393-7.

Abstract

BACKGROUND

Hypoxia inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Recently, two single nucleotide polymorphisms (SNPs) in the HIF-1 alpha gene, C1772T and G1790A, were shown to cause significantly higher transcriptional activity than did the wild-type. This study aimed to investigate the effect of these SNPs on the prognosis of colorectal cancer (CRC).

PATIENTS AND METHODS

DNA from 336 CRC patients was genotyped. Genotypes of each polymorphism were tested for association with disease-free survival (DFS) using univariate and multivariate Cox-regression analysis.

RESULTS

Genotype frequencies were: CC 75.6%, CT 18.8% and TT 1.8% for HIF1A1 C1772T and GG 93.2%, GA 2.7% and AA 0% for G1790A. A statistically significant association between DFS and clinicopathological features was observed. However, no association was found between HIF1A1 C1772T (p=0.44; risk ratio of recurrence, RR=1.19, 95% confidence interval, CI=0.77 to 1.83) and G1790A (p=0.89; RR=0.92, 95% CI=0.29 to 2.90) polymorphisms and DFS in univariate and multivariate Cox-regression analysis.

CONCLUSION

These results suggest that HIF1A1 C1772T and G1790A polymorphisms are not involved in the progression or metastasis of CRC.

摘要

背景

缺氧诱导因子-1(HIF-1)是细胞对缺氧反应的关键调节因子,在肿瘤生长中起核心作用。最近,HIF-1α基因中的两个单核苷酸多态性(SNPs)C1772T 和 G1790A 被证明比野生型具有更高的转录活性。本研究旨在探讨这些 SNPs 对结直肠癌(CRC)预后的影响。

患者和方法

对 336 例 CRC 患者的 DNA 进行基因分型。使用单变量和多变量 Cox 回归分析,检测每种多态性的基因型与无病生存(DFS)的相关性。

结果

HIF1A1 C1772T 的基因型频率为 CC 75.6%、CT 18.8%和 TT 1.8%,而 G1790A 的基因型频率为 GG 93.2%、GA 2.7%和 AA 0%。DFS 与临床病理特征之间存在统计学显著关联。然而,在单变量和多变量 Cox 回归分析中,均未发现 HIF1A1 C1772T(p=0.44;复发风险比,RR=1.19,95%置信区间,CI=0.77 至 1.83)和 G1790A(p=0.89;RR=0.92,95%CI=0.29 至 2.90)多态性与 DFS 之间存在相关性。

结论

这些结果表明,HIF1A1 C1772T 和 G1790A 多态性不参与 CRC 的进展或转移。

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