Vascular endothelial growth factor (VEGF) polymorphism is associated with prognosis of patients with gastric cancer

4019 Background: Recent studies demonstrated that the expression of vascular endothelial growth factor (VEGF) family had a prognostic significance in patients with gastric cancer. The present study analyzed VEGF polymorphism and its impact on prognosis in patients with gastric cancer. Methods: Five hundred three consecutive patients with surgically resected gastric adenocarcinoma at a single institution between January 2000 and December 2001 were enrolled into the study. Genomic DNA was extracted from paraffin-embedded tumor tissue and four VEGF (-460T > C, +405C > G, 936C> T, and -1154G > A) genotypes were determined using a PCR-RFLP assay. Results: The median age of patients was 60.0 years (range, 25–83 years), and 337 (67.0%) patients were male. Pathologic stages after resection were as follows: stage 0 (n=6, 1.2%), stage I (n=277, 55.1%), stage II (n=105, 20.9%), stage III (n=74, 14.7%), and stage IV (n=41, 8.2%). The estimated 5-year disease-free survival (DFS) rates according to stage were significantly different (p < 0.0001). Three VEGF polymorphisms (+405C > G, 936C, and -1154G > A > T) were not associated with survival of patients, while -460T > C polymorphism had a prognostic significance. In patients with early stage gastric cancer (stage 0 or 1, n=283), the estimated 5-year DFS and carcinoma-specific survival (CSS) for patients with homozygous genotype (CC or TT) of -460T > C were superior to those for heterozygous genotype (CT) (98.1% versus 90.3%, p=0.0047; 98.1% versus 92.5%, p=0.0284). In Cox multivariate regression, stage and VEGF -460T > C genotype were an independent prognostic factors for both DFS (p=0.007; p=0.010) and CSS (p=0.013; p=0.038). Conclusions: VEGF -460T > C polymorphism was found to be an independent prognostic marker for patients with curatively resected early stage gastric adenocarcinoma. Accordingly, VEGF -460T > C polymorphism can help to identify patients with unfavorable clinical outcome and thereby may be useful to refine therapeutic decisions in early stage gastric cancer. No significant financial relationships to disclose.