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

Abstract

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.

Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab

“…As a confirmation of preclinical findings, genotypes determining a higher VEGF secretion have been found in humans to be associated with increased risk of prostate, bladder, lung, colorectal, ovarian, and breast cancer diagnosis or relapse [9][10][11][12][13][14].…”

“…Median number of treatment cycles administered was 7 (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Dose reduction (>25% of the planned dose for any of the drug for two or more cycles) or treatment delay (>1 week of delay for two or more cycles) was necessary in eight patients (20%).…”

“…Moreover, VEGF SNPs may have a prognostic value for non-small cell lung, colorectal, ovarian, and breast cancer patients [11][12][13][14].…”

Antiangiogenic drugs in ovarian cancer

“…Several retrospective clinical studies in ovarian cancer have also demonstrated that intratumoral VEGF and VEGFR-2 expression and the carriage of VEGF gene polymorphisms associated with an increased VEGF excretion are independent poor prognostic factors (Shen et al, 2000;Goodheart et al, 2005;Hefler et al, 2007).…”

Role of five small nucleotide polymorphisms in the VEGF gene on the susceptibility to osteosarcoma and overall survival of patients

“…Previous studies have reported that -634G/C polymorphism is associated with the clinical outcome of breast, gastric, prostate and ovarian cancers (33)(34)(35)(36). One study investigated the association between VEGF polymorphism and the prognosis of osteosarcoma, but this previous study did not identify that the -634G/C polymorphism played a role in the clinical outcome of osteosarcoma (37). Additional studies are required to confirm the association between this polymorphism and osteosarcoma.…”