Hefler Lukas A, Mustea Alexander, Könsgen Dominique, Concin Nicole, Tanner Berno, Strick Reiner, Heinze Georg, Grimm Christoph, Schuster Eva, Tempfer Clemens, Reinthaller Alexander, Zeillinger Robert
Department of Obstetrics and Gynecology and Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Austria.
Clin Cancer Res. 2007 Feb 1;13(3):898-901. doi: 10.1158/1078-0432.CCR-06-1008.
Vascular endothelial growth factor (VEGF), an important regulator of angiogenesis and vascular permeability, is involved in various steps of ovarian carcinogenesis. Gene polymorphisms within the gene encoding VEGF were shown to be independently associated with an adverse outcome in various malignancies. No data are available for ovarian cancer.
In the present multicenter study, we examined three common polymorphisms within the VEGF gene (-634G/C, -1154G/A, and -2578C/A) known to be associated with an increased VEGF production in 563 Caucasian patients with ovarian cancer from Austria and Germany using pyrosequencing. Results were correlated with clinical data.
The three investigated polymorphisms did not correlate with any of the investigated clinicopathologic variables. In univariate and multivariate models, no significant correlations between any polymorphism and patients' overall survival were ascertained. Simultaneous carriage of the three homozygous genotypes (i.e., VEGF -634C/C, VEGF -1154G/G, VEGF -2578C/C) known to be associated with increased VEGF expression in an individual patient, however, was independently associated with a shortened overall survival (hazard ratio, 2.1; 95% confidence interval, 1.1-3.9; P=0.02).
We present the first data on VEGF gene polymorphisms in ovarian cancer. Simultaneous carriage of the three investigated homozygous genotypes was shown to be an independent adverse prognosticator of overall survival.
血管内皮生长因子（VEGF）是血管生成和血管通透性的重要调节因子，参与卵巢癌发生的各个阶段。编码VEGF的基因内的基因多态性已被证明与多种恶性肿瘤的不良预后独立相关。目前尚无关于卵巢癌的相关数据。
在本多中心研究中，我们使用焦磷酸测序法检测了来自奥地利和德国的563例白人卵巢癌患者中VEGF基因内已知与VEGF产生增加相关的三种常见多态性（-634G/C、-1154G/A和-2578C/A）。结果与临床数据相关联。
所研究的三种多态性与任何所研究的临床病理变量均无相关性。在单变量和多变量模型中，未确定任何多态性与患者总生存期之间存在显著相关性。然而，已知在个体患者中与VEGF表达增加相关的三种纯合基因型（即VEGF -634C/C、VEGF -1154G/G、VEGF -2578C/C）同时存在与总生存期缩短独立相关（风险比，2.1；95%置信区间，1.1 - 3.9；P = 0.02）。
我们提供了关于卵巢癌VEGF基因多态性的首批数据。所研究的三种纯合基因型同时存在被证明是总生存期的独立不良预后指标。
