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Vascular Endothelial Growth Factor (VEGF) Polymorphisms and Serum VEGF Levels in Women With Epithelial Ovarian Cancer, Benign Tumors, and Healthy Ovaries
  1. Blanca González-Palomares, MD*,
  2. Pluvio J. Coronado Martín, MD, PhD*,
  3. María Luisa Maestro de las Casas, PhD,
  4. Silvia Veganzones de Castro, PhD,
  5. Sara Rafael Fernández, PhD,
  6. Marta Vidaurreta Lázaro, PhD,
  7. Virginia De la Orden García, PhD and
  8. Jose Antonio Vidart Aragon, MD, PhD*
  1. * Department of Obstetrics and Gynecology and
  2. Service of Clinical Analyses, Hospital Clínico San Carlos, Complutense University of Madrid, Madrid, Spain.
  1. Address correspondence and reprint requests to Blanca González Palomares, MD, Department of Obstetrics and Gynecology, Hospital Clínico San Carlos, C/Profesor Martín Lagos S/N, 28040 Madrid, Spain. E-mail: bgonzalezpalomares{at}gmail.com.

Abstract

Objective This study analyzed the relation of 5 single-nucleotide polymorphisms (SNPs) in the VEGF (vascular endothelial growth factor) gene in patients with epithelial ovarian cancer (EOC), compared with patients carrying benign tumors or healthy ovaries. We studied serum VEGF levels and the relation with SNPs and association between VEGF SNPs and haplotypes with progression-free survival (PFS) in patients with cancer.

Methods The genotyping of VEGF gene polymorphisms (−2578 C/A, −1154 G/A, −460 T/C, +405 G/C, +936 C/T) was performed in DNA isolated from blood samples of 100 women. The different genotypes were evaluated by quantitative real-time polymerase chain reaction. Vascular endothelial growth factor protein concentration was assessed in serum using solid-phase sandwich enzyme-linked immunosorbent assay.

Results We found statistically significant differences in the distribution of VEGF genotypes among the 3 groups of patients: −2578 C/A between those with EOC and healthy ovary (P = 0.04), −460 T/C between those with EOC and healthy ovary (P = 0.03), and −460 T/C between those with benign tumors and healthy ovary (P = 0.02). Vascular endothelial growth factor serum levels were analyzed in patients with EOC. Higher levels were found in patients with clear cell carcinoma compared with those with serous, mucinous, or endometrioid tumors (P < 0.05). No clear association was observed between VEGF SNPs and serum VEGF levels. There was no significant correlation between VEGF SNPs and PFS. In haplotype analysis, CGTCT and CGTGT showed worse prognosis without reaching the statistical significance. CGCGC and AGTGC haplotypes had statistically significant differences among patients with EOC, benign tumors, and healthy ovaries (Ps = 0.046 and 0.041, respectively).

Conclusions The distribution of VEGF genotypes was different in patients with EOC, compared with those with benign tumors or women with healthy ovaries. Vascular endothelial growth factor serum levels were higher in patients with clear cell carcinoma. No correlation was found with improved PFS, but CGTCT and CGTGT haplotypes showed worse prognosis.

  • Ovarian cancer
  • VEGF polymorphisms
  • Serum VEGF
  • Haplotype
  • Survival

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Footnotes

  • The authors declare no conflicts of interest.

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