Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms - A case-control study in an Omani population

Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis, tumor growth, and metastasis. We investigated the associations between VEGF gene polymorphisms and gastric cancer (GC) risk predisposition and prognostic characteristics in an Omani population, an ethnic group which has not been studied previously. We analyzed three VEGF polymorphisms (+405 G/C, -460 T/C, and +936 C/T) by the extraction of genomic DNA from peripheral blood of 130 GC patients and 130 control subjects followed by VEGF genotyping using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. There were no significant associations between the VEGF polymorphisms and GC risk. There were significant correlations between the +405 C/C genotype and both poor tumor differentiation (P = 0.007) and lymph node metastasis (P = 0.03) and between the +460 T/T genotype and poor tumor differentiation (P = 0.03) with a statistical trend toward lymph node involvement (P = 0.05). VEGF gene polymorphisms had no significant effects on survival, but the VEGF +405 G/G genotype had a statistical trend toward lower survival rate with a hazard ratio of 1.6 [95% CI, 0.9-2.9] compared with the VEGF +405 CC/GC combined genotype (P = 0.049). Multivariate analysis showed that disease stage at diagnosis and the +405 G/G genotype were independent variables of adverse prognostic significance. There were no associations between the six common haplotypes identified and both GC risk predisposition and survival. The current study suggests that VEGF polymorphisms have no role in GC risk predisposition, but may have prognostic significance in GC patients.