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

Document Type: Research Articles

Authors

1 Division of Cancer Molecular Genetics, Prince Fahd Bin Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.

2 Department of surgical oncology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia.

3 Department of Microbiology, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia.

4 Breast Division, Department of Surgery, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia.

5 Prince Sultan Oncology Center, King Salman Armed Force Hospital, Tabuk, Saudi Arabia.

6 Department of Surgery Breast and Endocrine Unit, King Salman Armed Force Hospital, Tabuk, Saudi Arabia.

Abstract

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.

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