Prevalence of BRCA1 and BRCA2 Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer

Abstract

Background Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC. Materials and Methods Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis. Results Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor. Conclusion Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.

La lucha contra el cáncer de mama: una revisión sistemática sobre la prevalencia del BRCA en Colombia

“…Para concluir, es importante destacar los resultados obtenidos por Vargas y sus colaboradores, al margen de dos investigaciones distintas (Vargas et al, 2019(Vargas et al, , 2022, los cuales encontraron una asociación racial más relevante con la mutación del gen BRCA1 A1708E, la cual también se identificó en poblaciones afro.…”

“…Las tasas de incidencia y mortalidad estandarizadas por edad de 35,7 y 10,8 casos por 100.000 personas al año (Torres et al, 2007). Además, a nivel mundial, este tipo de cáncer es el más frecuente en mujeres y supone un gran problema de salud pública en el ámbito mundial (Briceño-Balcázar et al, 2017;Tuazon et al, 2020;Vargas et al, 2022).…”

Relação entre as mutações genéticas e a incidência do câncer de mama: revisão bibliográfica

“…22. Vargas et al, 2022. Prevalence of BRCA1 and BRCA2 Germline Mutations in Patients of African Descent with Early-Onset and Familial Colombian Breast Cancer.…”