Frequency Of BRCA1 Polymorphisms (rs799917 and rs1799966) Among Nigerian Breast Cancer Patients

Abstract

Breast cancer (BCa) is the most diagnosed malignancy among women worldwide, with an estimated 2.3 million new cases and 666,103 deaths recorded in 2022. In Nigeria, BCa remains the leading cause of cancer-related mortality among women, accounting for 32,278 (25.3%) new cases and 16,322 (20.5%) deaths in 2022. Breast cancer gene 1 (BRCA1) is a tumour suppressor gene involved in DNA damage repair, cell cycle regulation, and maintenance of genome stability. Studies suggest that genetic factors, such as Single Nucleotide Polymorphism (SNPs) in the BRCA1 genes, play a pivotal role in the development of cancers. The BRCA1 gene harbors specific SNPs within its coding sequence, including rs799917 and rs1799966. These SNPs interfere with the interaction between BRCA1 mRNA and miR-638, significantly decreasing BRCA1 expression among individuals carrying these variants. Several studies have reported correlations between BRCA1 polymorphisms rs799917 and rs1799966 with the risk of BCa. However, this relationship remains controversial. This study assesses the frequency of BRCA1 rs799917 and rs1799966 polymorphisms and their association with BCa in Nigeria. The case-control study included 500 BCa patients and 200 paired healthy controls. TaqMan genotyping assay was used to determine the genotypes of rs799917 and rs1799966 polymorphisms. Using logistic regression and Pearson's chi-square test, a statistically significant difference (p < 0.05) was identified in the genotype frequencies. The G allele of rs799917(p= 0.017; OR: 1.39) showed significant associations with the risk of breast cancer in Nigeria and, while globally reported as the wild-type allele, is observed as the variant allele in our population. The C Allele of rs1799966 confers a protective risk against breast cancer. Further study should focus on functional genomics to evaluate the interaction between miR-638 and the mRNA in individuals carrying this SNP, particularly in the Nigerian population. Keywords: breast