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.

A Germline Mutation in the BRCA1 3'UTR Variant Predicts Susceptibility to Breast Cancer in a Saudi Arabian Population

Purpose: The impact of the BRCA1-3'UTR-variant on BRCA1 gene expression and altered responses to external stimuli was previously tested in vitro using a luciferase reporter assay. Its ability to predict breast cancer risk in women was also assessed but the conclusions were inconsistent. The present study concerns the relationship between the BRCA1-3'UTR germline variant rs8176318G>T and susceptibility to Breast cancer in an ethnic population of Saudi Arabia. Methodology: The study included 100 breast cancer patients and 100 sex matched healthy controls from the northwestern region (Tabuk) and Dammam of Saudi Arabia were investigated for the BRCA1-3'UTR germline variant rs8176318G>T using an allele specific PCR technique. Genotype distributions were then compared. Results: The frequencies of the three genotypes GG, TT and GT in our Saudi Arabian patients were 26%, 8% and 66% and in healthy controls were 45%, 5% and 50%, respectively (p=0.03). Risk of developing breast cancer was found to be significantly associated with the GT variant (OR 2.28, 1.24-4.191; RR 1.47, 1.11-1.93; P=0.007), GT+TT (OR, 2.32, 1.28-4.22; RR 1.48, 1.13-1.94; P=0.005) and the T allele (OR 1.62 , 1.072- 2.45; RR 1.28, 1.02-1.60: P=0.020). There were 2.76 and 2.28 fold increase risks of developing breast cancer associated with the TT and GT genotypes in our cases. A significant correlation was also found between the BRCA1 3'UTR variants with the stage of the disease and distant metastasis but not with age, grade, and ER, PR and her2/neu status. Conclusion : The rs8176318G/T in the 3'untranslated region (UTR) of the BRCA1 gene was found to be associatedwith increased susceptibility to breast cancer in our study population, increased risk being noted with the GT and TT genotypes. Further association studies are needed to confirm this finding in other regions of Saudi Arabia.