BRCA1 rs799917 and rs1799966 Variants and Breast Cancer Risk in Nigerian Women: A Case-Control Study With Population-Based Allele Frequency Analysis.

IntroductionBRCA1 is a tumor suppressor gene involved in DNA repair, genomic stability, and cell cycle regulation. The BRCA1 single nucleotide polymorphisms (SNPs) rs799917 and rs1799966 have been widely investigated for their association with breast cancer (BCa) risk, with inconsistent and population-specific findings. However, their frequency and clinical relevance in Nigerian populations remain poorly characterized. This study evaluated their association with BCa risk in Nigerian women and interpreted these findings within a global context of allele frequency variation.MethodsThis prospective case-control study recruited 379 BCa cases and 196 age-matched controls. The samples were genotyped for BRCA1 rs799917 (A/G) and rs1799966 (C/T) using TaqMan real-time polymerase chain reaction (PCR). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Allele frequencies from population-specific datasets in the database of single nucleotide polymorphism (dbSNP) were extracted and combined in a meta-analysis to compare variant distribution across global populations.ResultsNo significant association was observed between BRCA1 variants (rs799917 and rs1799966) and BCa risk in this cohort. Genotype distributions were comparable between cases and controls, and none of the tested genetic models reached statistical significance. Meta-analysis revealed marked inter-population variation in allele frequencies. Africans showed the lowest frequency of the rs799917 G allele (13.8%), and the highest frequency of the A allele (86.36%), whereas Europeans showed the highest G allele frequency (65.92%). For rs1799966, Africans had the lowest C allele frequency (20.17%) and highest T allele frequency (79.8%), while Asians showed the highest C frequency (38.25%).ConclusionBRCA1 variants rs79917 and rs1799966 were not associated with BCa susceptibility in this Nigerian cohort. The observed inter-population differences in allele frequencies highlight the importance of genetic diversity in understanding BCa risk.