Potential Impact of Vascular Endothelial Growth Factor Gene Variation (-2578C>A) on Breast Cancer Susceptibility in Saudi Arabia: a Case-Control Study

AIM: VEGF gene polymorphisms can induce either increase or inhibition of VEGF secretion, with altered promoter activity. The VEGF rs699947 SNP is located in the promoter region and is associated with susceptibility to breast carcinoma development. Here, we investigated the association of the -2578C>A polymorphism in the VEGF gene with breast cancer risk in Saudi women. METHODOLOGY: Genotyping of the VEGF-gene variation (-2578A>C) was performed using the amplification refractory mutation system PCR. We investigated the association of VEGF gene variants with different clinicopathological features of breast cancer patients. RESULTS: A significant difference was observed in genotype distribution among the breast cancer cases and sex matched healthy controls (p=0.03). The frequencies of the three genotypes CC, CA, AA found in the patient samples were 37%, 45% and 18% and in the healthy controls were 54%,37%, and 09% respectively. An increased risk of developing breast cancer in Saudi women was associated with the VEGF −2578 AA genotype (OR = 2.91, 95 % CI, 1.18-7.20; p = 0.01; RR 1.78 (1.01-3.11 p=0.01), the VEGF −2578 A allele (OR = 1.79, 95 % CI, 1.17-2.73; p = 0.004: RR 1.35 1.07-1.71) and the VEGFR-(CA+ AA) (OR 1.99 1.13-3.51; RR 1.401.0-1.85). Thus the A allele increased the risk of BC when compared with C allele. When we stratified groups of patients according to the status of tumor markers, stage, age and metastasis, statistically significant associations with −2578 C/A SNP were revealed. CONCLUSION: Our data showed a significant association of the VEGF -2578C>A polymorphism with BC susceptibility in Saudi women. The VEGF -2578AA homozygote significantly increases the risk and can be useful as a predisposing genetic marker. Further studies with larger sample sizes are necessary to confirm our findings.