Vascular endothelial growth factor (VEGF) gene polymorphisms associated with prognosis for patients with colorectal cancer

Abstract

4125 Background: Vascular endothelial growth factor (VEGF) or its family may be considered to play an important role in lymphangiogenesis and lymphatic tumor spread, thereby affecting prognosis of colorectal cancer. Accordingly, the present study analyzed VEGF gene polymorphisms and their impact on the prognosis for patients with colorectal cancer. Patients and Methods: Four hundred and sixty-five consecutive patients with surgically treated colorectal adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from fresh colorectal tumor tissue and 3 VEGF (-2578C > A, -634G > C, and +936C > T) gene polymorphisms determined using a PCR/DHPLC (Polymerase chain reaction/Denaturing high-performance liquid chromatography) assay. Results: The median age of the patients was 64 years (range, 21–89), and 264 (56.7%) patients had colon cancer and 201 (48.2%) patients rectal cancer. Pathologic stages evaluable (n=464) after surgery were as follows: stage I (n=79, 17.0%), stage II (n=157, 33.8%), stage III (n=157, 33.8%), and stage IV (n=71, 15.3%). Multivariate survival analysis including stage, differentiation, and CEA level showed that survival for patients with the -634CC (overall survival [OS]: hazard ratio [HR]=0.175, P<0.001; progression-free survival [PFS]: HR=0.554, P=0.040) or GC genotype (OS: HR=0.158, P<0.001; PFS: HR=0.630, P=0.044) were better than for patients with the -634GG genotype, whereas the +936TT (OS: HR=65.959, P<0.001; PFS: HR=2.823, P=0.016) or CT genotype (OS: HR=16.116, P<0.001; PFS: HR=3.507, P<0.001) were associated with a worse survival compared to the CC genotype. In haplotype analysis, the -2578A/-634G/+936T haplotype exhibited a significantly worse survival when compared to the wild -2578C/-634G/+936C haplotype (OS: HR=4.670, P<0.001; PFS: HR=3.624, P<0.001). Conclusions: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with colorectal cancer. Accordingly, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome. No significant financial relationships to disclose.