Vascular endothelial growth factor (VEGF) polymorphisms and outcome of epithelial ovarian cancer patients

Background

Angiogenesis (AG), with participation of vascular endothelial growth factor (VEGF), is a crucial process involved in tumor growth, formation of metastasis, and patientś outcome. VEGF was crucially involved in epithelial ovarian cancer (EOC) carcinogenesis. The VEGF is encoded by the VEGF polymorphic gene. The wild-type alleles of VEGF c.-2595C > A (rs699947) and c.-1154G > A (rs1570360), and the variant allele of VEGF c.-460C > T (rs833061) polymorphisms were associated with higher VEGF production than the remaining alleles. We aimed to analyze herein the roles of these SNPs in outcome of EOC patients.

Methods

Our analysis included 85 EOC patients seen at diagnosis seen from 1996 to 2007 (median age: 53 years; tumor of type I: 56, type II: 29; tumor at stage I: 37, stages II to IV: 48). Patients were treated with tumour resection and cisplatin-based chemotherapy. DNA from peripheral blood was analyzed by real-time polymerase chain reaction for genotyping of the polymorphisms. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and curves were compared by the log-rank test. The Cox hazards model was used to identify prognostic variables influencing survival in univariate analysis, and significant results were validated using a bootstrap resembling study to investigate the stability of risk estimates (1,000 replications).

Results

The median follow-up was 96 months. At 24 months of follow-up, PFS was shorter in patients with 50 years or more (71.6% versus 89.2%, P= 0.01), tumour of type II (62.1% versus 86.8%, P= 0.02) and at stage II to IV (63.6% versus 97.5%, P= 0.0001), and VEGF c.2578 CC genotype (72.4% versus 90.5%, P= 0.04) compared to others. OS was shorter in patients with tumour of type II (75.9% versus 93.3%, P= 0.009) and at stage II to IV (79.5% versus 97.5%, P= 0.0001) at this time. Patients with the VEGF c.2578 CC genotype had 2.15 more chances of presenting disease progression than others. Differences between groups remained the same in univariate Cox analysis, and were validated by the bootstrap study.

Conclusions

Our data suggest that inherited abnormality in AG pathway, related to VEGF c.-2578C > A SNP, acts as a prognostic factor in EOC.

Clinical trial identification

Legal entity responsible for the study

UNICAMP

Funding

UNICAMP

Disclosure

All authors have declared no conflicts of interest.