Genetic Variability and Differentiation of the BRCA1 and BRCA2 Genes in Female Breast Cancer in Senegal

Abstract

Breast cancer constitutes a major public health problem. In Senegal, this pathology ranks second in terms of incidence and third in terms of mortality among cancers. BRCA1 and BRCA2 are two susceptibility genes for breast and/or ovarian cancer, implicated in hereditary breast cancer cases. These genes have been the subject of extensive research in the context of germline mutations; however, data on their role in sporadic breast cancer, particularly in sub-Saharan African populations such as Senegal, remain scarce or unavailable. To address this gap, the present study analyzed 51 surgical specimens of healthy and cancerous breast tissue to characterize the genotypic profile of BRCA mutations in Senegalese women. Three loci corresponding to founder mutations described in the Ashkenazi Jewish population BRCA1-185delAG, BRCA1-5382insC, and BRCA2-6174delT were targeted. The objectives were to determine the genotypic profile of each population at each locus and assess potential differences, to test genetic equilibrium, and to evaluate genetic differentiation between BRCA1- and BRCA2-associated breast cancer. Comparison of wild-type and mutant allele profiles between the two tissue types revealed no significant difference. Analysis of genetic diversity between healthy and cancerous tissues showed a heterozygote excess at both BRCA1 loci and a heterozygote deficit at the BRCA2 locus. Low genetic differentiation was observed between control and tumor tissues, attributable to the BRCA1-185delAG mutation, with an Fst value of 0.0072. These findings suggest that the BRCA1-185delAG mutation, despite its low penetrance, may be implicated in breast cancer among Senegalese women.