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

Abstract

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