Pathogenic variants in BRCA1 and BRCA2 genes associated with female breast and ovarian cancer in the Mexican population

Abstract

Breast and ovarian cancers are significant global health challenges, with inherited variations in breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) substantially increasing the risk, aggressiveness, and early onset of these diseases. This work aimed to examine pathogenic variants (PVs) in BRCA1 and BRCA2 databases that include Mexican populations. A systematic review of literature and data mining spanning from 2002 to 2023 was conducted. Articles published in journals indexed in SCImago quartiles Q1 to Q4 were screened. Databases were paired, standardized, and enriched with data from reputable global platforms: Genome Data Viewer, dbSNP, ClinVar, gnomAD browser, Breast Cancer Information Core (BIC), ClinGen, Varsome, Human Genome Variation Society (HGVS), Bioproject, Ensembl, Gene NIH NCIB, UniProt, and BRCA Exchange. Outcomes included data from 9,026 Mexican genotypes, identifying 657 PVs. Genetic mapping revealed certain exons, notably exon 10 of BRCA1 and exon 11 of BRCA2, as highly mutagenic hot spots. The most frequent alteration was a large deletion in BRCA1 (ex9-12del), associated with a founder effect originating from a common Mexican ancestor. Finally, we constructed a genetic map containing all the single nucleotide variants (SNVs) and large rearrangements presented in the analyzed databases.