The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cell carcinoma
The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cell carcinoma
复制标题
VHL和HIF1A基因的多态性与肾细胞癌的预后相关，但与肾细胞癌的发展无关。
DOI：
10.1093/annonc/mdr325
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发表时间：
2012-04-01
影响因子：
50.5
通讯作者：
Zhang, Z.
中科院分区：
文献类型：
--
作者：
Qin, C.;Cao, Q.;Zhang, Z.
背景：von Hippel-Lindau （VHL）肿瘤抑制基因和缺氧诱导因子-1 α (HIF1A)在肾癌发生中起关键作用。本研究旨在阐明VHL和HIF1A多态性对肾细胞癌（RCC）易感性和生存率的影响。研究对象和方法：我们对4个可能具有功能的单核苷酸多态性（VHL中的rs779805， HIF1A中的rs11549465、rs11549467和rs2057482）进行了基因分型，并在一项包含620例患者和623例对照的病例对照研究中评估了它们与RCC风险、临床病理参数以及311例队列中RCC预后的相关性。结果：在RCC病例和对照组之间，VHL和HIF1A基因型无显著差异。然而，4种多态性中>= 2变异等位基因的个体与较少的淋巴结转移和较低的临床分期相关（P = 0.032和P = 0.041）。变异等位基因数量与生存率呈剂量-反应关系（P-trend = 0.013）。此外，多因素Cox回归分析显示，变异等位基因数量（>= 1 vs .0）与临床分期和肿瘤分级一起是影响RCC生存的独立预后因素（P = 0.036）。结论：VHL和HIF1A多态性可能不影响RCC易感性，但可能共同影响RCC的进展和生存。
Background: The von Hippel-Lindau (VHL) tumor suppressor gene and hypoxia-inducible factor-1 alpha (HIF1A) play a pivotal role in renal carcinogenesis. This study was aimed to clarify the influence of VHL and HIF1A polymorphisms on renal cell cancer (RCC) susceptibility and survival.Subjects and methods: We genotyped four potentially functional single-nucleotide polymorphisms (rs779805 in VHL and rs11549465, rs11549467, and rs2057482 in HIF1A) and assessed their associations with RCC risk, clinicopathologic parameters in a case-control study of 620 patients and 623 controls, and the prognosis of RCC in a cohort of 311 patients.Results: No significant differences in VHL or HIF1A genotypes were observed between RCC cases and controls. However, individuals with >= 2 variant alleles of the four polymorphisms were associated with less frequent lymph node metastasis and lower clinical stage (P = 0.032 and P = 0.041, respectively). And the number of variant alleles was associated with improved survival in a dose-response manner (P-trend = 0.013). Furthermore, multivariate Cox regression analysis showed that the number of variant alleles (>= 1 versus 0) was an independent prognostic factor for RCC survival (P = 0.036) together with clinical stage and tumor grade.Conclusion: The VHL and HIF1A polymorphisms may not influence RCC susceptibility but may jointly influence RCC progression and survival.