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Vascular Endothelial Growth Factor Gene Polymorphisms Are Associated with Prognosis in Ovarian Cancer

Authors' Affiliations: ¹ Department of Obstetrics and Gynecology and ² Core Unit for Medical Statistics and Informatics, Medical University of Vienna; ³ Ludwig Boltzmann Institute for Gynecology and Gynecological Oncology, Vienna, Austria; ⁴ Department of Obstetrics and Gynecology, Charité/Campus Virchow-Klinikum, University Medicine of Berlin, Germany; ⁵ Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria; ⁶ Department of Obstetrics and Gynecology, Johannes Gutenberg-University, Mainz, Germany; and ⁷ Department of Obstetrics and Gynecology, Friedrich-Alexander-University Erlangen-Nuernberg, Erlangen, Germany

Requests for reprints: Lukas Hefler, Department of Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400-2962; Fax: 43-1-40400-2911; E-mail: lukas.hefler{at}meduniwien.ac.at.

Purpose: 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.

Experimental Design: 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.

Results: 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).

Conclusions: 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.

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