Polymorphisms of HIF1A gene are associated with prognosis of early stage non-small-cell lung cancer patients after surgery.
Polymorphisms of HIF1A gene are associated with prognosis of early stage non-small-cell lung cancer patients after surgery.
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DOI：
10.1007/s12032-014-0877-8
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Su H
中科院分区：
文献类型：
--
作者：
Liu B;Liu Q;Song Y;Li X;Wang Y;Wan S;Zhang Z;Su H
缺氧诱导因子1 α（HIF 1 α）激活参与血管生成和细胞存活的基因的转录。肿瘤内缺氧引起的HIF 1 α过表达及其基因改变与包括非小细胞肺癌（NSCLC）在内的几种癌症类型的死亡率增加相关。本研究旨在探讨HIF 1A基因单核苷酸多态性（SNPs）对NSCLC预后的预测作用。我们对HIF 1A基因中的两个功能性SNP（rs 2057482和rs 2301113）进行了基因分型，并通过考克斯比例风险模型评估了它们与494例非小细胞肺癌患者临床病理参数和预后的相关性。对于总体分析，SNPs与NSCLC临床结局之间无显著相关性。然而，在早期NSCLC患者（I/II期）的分层分析中，我们观察到rs2057482变异基因型在显性模型中对总生存期（OS）（HR 0.42，95% CI 0.22 - 0.80）和无复发生存期（RFS）（HR 0.60，95% CI 0.36 - 0.97）具有保护作用。此外，基于显性模型的多变量考克斯分析表明，在携带rs2301113变异基因型的早期T期（T1和T2）肿瘤患者中，以及在rs2057482无淋巴结受累（N0期）患者中，观察到死亡和复发风险显著增加。HIF 1A基因变异与早期NSCLC患者的预后显著相关。本文的在线版本（doi：10.1007/s12032 - 014 - 0877 - 8）包含补充材料，可供授权用户使用。
Hypoxia-inducible factor 1α (HIF1α) activates the transcription of genes that are involved in angiogenesis and cell survival. Over-expression of HIF1α caused by intratumoral hypoxia and its genetic alterations are associated with increased mortality in several cancer types including non-small-cell lung cancer (NSCLC). The aim of this study was to investigate the predictive role of single nucleotide polymorphisms (SNPs) in HIF1A gene in NSCLC outcomes. We genotyped two functional SNPs (rs2057482 and rs2301113) in HIF1A gene and assessed their associations with clinicopathological parameters and prognosis of 494 NSCLC patients by Cox proportional hazard model. There was no significant association between the SNPs and clinical outcomes of NSCLC for overall analysis. However, in stratified analysis for NSCLC patients at early stage (I/II), we observed a protective effect conferred by variant genotype of rs2057482 on overall survival (OS) (HR 0.42, 95 % CI 0.22–0.80) and recurrence-free survival (RFS) (HR 0.60, 95 % CI 0.36–0.97) in a dominant model. Additionally, multivariate Cox analysis based on dominant model indicated that significant increased death and recurrence risks were observed in patients with early T-stage (T1 and T2) tumors, who carrying variant-containing genotype of rs2301113, as well as in patients without lymph node involvement (N0 stage) for rs2057482. Genetic variations on HIF1A gene are significantly associated with NSCLC outcomes in patients with early stage disease. The online version of this article (doi:10.1007/s12032-014-0877-8) contains supplementary material, which is available to authorized users.
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