Prevalence ofBRCA1andBRCA2Germline 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).…”

Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients

“…Additionally, within the same population, such as Brazil, there is high variability in the mutation frequencies of the BRCA genes (10.1% vs 22.4%), supporting the observation that the genetic background of Latin American populations results from events leading to unique population structures within and between countries [ 14 – 16 ]. Specifically, the highest frequencies for the BRCA genes reported in the Latin American population are described in patients with breast and ovarian cancer from Afro-Colombian families, in whom 33.3% of pathogenic variants were identified [ 17 ], demonstrating the impact of patient selection criteria on the variability of reported data.…”

“…In Colombia, previous reports described mutations in BRCA1/2 genes focused on hereditary/familial cases [ 17 , 21 , 26 , 27 ]. Even though, few studies analyzed mutation prevalence in BRCA1/ 2 genes from unselected BC patients, finding that their frequency ranges from 0.4 to 3.3% [ 20 , 21 ], which is concordant with our results, since the frequency of women with mutations in BRCA1/2 is 3.25%.…”

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.…”