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Potential Impact of Vascular Endothelial Growth Factor Gene Variation (-2578C>A) on Breast Cancer Susceptibility in Saudi Arabia: a Case-Control Study
Authors:Ibrahim Abdullah  Al BalawiRashid  MirF M  Abu-Duhier
Affiliation:1Department of Surgical Oncology, Faculty of Medicine, University of Tabuk, Kingdom of Saudi Arabia.2Prince 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 promoteractivity. The VEGF rs699947 SNP is located in the promoter region and is associated with susceptibility to breastcarcinoma development. Here, we investigated the association of the -2578C>A polymorphism in the VEGF gene withbreast cancer risk in Saudi women. Methodology: Genotyping of the VEGF-gene variation (-2578A>C) was performedusing the amplification refractory mutation system PCR. We investigated the association of VEGF gene variants withdifferent clinicopathological features of breast cancer patients. Results: A significant difference was observed ingenotype distribution among the breast cancer cases and sex matched healthy controls (p=0.03). The frequencies of thethree genotypes CC, CA, AA found in the patient samples were 37%, 45% and 18% and in the healthy controls were54%,37% ,and 09% respectively. An increased risk of developing breast cancer in Saudi women was associated withthe 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 −2578A 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 groupsof patients according to the status of tumor markers, stage, age and metastasis, statistically significant associationswith −2578 C/A SNP were revealed. Conclusion: Our data showed a significant association of the VEGF -2578C>Apolymorphism with BC susceptibility in Saudi women. The VEGF -2578AA homozygote significantly increases therisk and can be useful as a predisposing genetic marker. Further studies with larger sample sizes are necessary toconfirm our findings.
Keywords:VEGF-Vascular endothelial growth factor  SNP- Single-nucleotide polymorphism  UTR-Untranslated region  ARMS-Amplification refractory mutation system  OR-Odds ratio
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