The relationship of VEGF polymorphisms with serum VEGF levels and progression-free survival in patients with epithelial ovarian cancer.
OBJECTIVE
The vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability of tumors. In the present study we evaluated the relation of five single nucleotide polymorphisms (SNPs) in the VEGF gene with progression-free survival. Furthermore, we evaluated the functional significance of the SNPs as determined by the influence on serum VEGF levels in ovarian cancer.


METHODS
Serum from 143 consecutive ovarian cancer patients referred for first line platinum/paclitaxel treatment were analyzed for serum VEGF levels using commercially available enzyme-linked immunosorbent assay (ELISA). VEGF gene polymorphisms (-2578 C/A, -1154 G/A, -460 T/C, +405 G/C and +936C/T) were determined by real time PCR using genomic DNA extracted from whole blood samples.


RESULTS
VEGF serum levels were significantly higher in carriers of the 2578C, 460T and 405C, alleles compared to non-carriers (p=0.003, p=0.003 and p=0.001, respectively). There was no significant correlation between VEGF SNP genotypes and progression-free survival. In haplotype analysis, the multivariate survival analysis showed that progression-free survival (PFS) for the patients with the AGCGC haplotype was significantly improved compared to patients with other haplotypes (HR 1.9, p=0.036).


CONCLUSIONS
VEGF polymorphisms were found to be significantly related with serum VEGF levels. The AGCGC haplotype was found to be independently associated with improved PFS.
Steffensen
K D
KD
Department of Oncology, Vejle Hospital, Vejle, Denmark. Karina.Dahl.Steffensen@slb.regionsyddanmark.dk
Waldstrøm
M
M
Brandslund
Ivan
I
Jakobsen
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016190:Carboplatin; D017239:Paclitaxel