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

Document Type: Research Articles

Authors

1 Department of Surgical Oncology, Faculty of Medicine, University of Tabuk, Kingdom of Saudi Arabia.

2 Prince Fahd Bin Sultan Research Chair, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Kingdom of Saudi Arabia.

Abstract

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.

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