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. 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. 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. 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.

Background: Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common BRCA1/2 founder mutations have previously been identified. Because nothing is known about the contribution of BRCA1/2 germline mutations to early-onset and hereditary breast and/or ovarian cancer in Afro-Colombians, we conducted the first study on 60 patients with early-onset and familial breast cancer in this population. Materials and Methods: Screening for the four Colombian founder mutations BRCA1/c.3331_3334delCAAG, BRCA1/c.5123C>A, BRCA2/c.2806_2809delAAAC, and BRCA2/c.1763_1766delATAA was performed using mismatch polymerase chain reaction (PCR) analysis, PCR-based restriction fragment length polymorphism analysis, and qualitative real-time PCR. Mutations were confirmed by direct DNA sequencing. Results: The BRCA1 founder mutation c.5123C>A was identified in one family with breast and ovarian cancer (1/60, 1.7%). Three women were diagnosed with breast cancer, including one with bilateral disease, at the ages of 30, 30/33, and 52 years, and one woman was diagnosed with ovarian cancer at the age of 60 years. Conclusion: Our data showed a low prevalence of the BRCA1/2 founder mutations in Colombians of African descent, implying that these mutations should not be recommended for genetic screening programs in the Afro-Colombian population.

Background: Genetic variants in microRNA (miR) binding sites affect the regulation of miR-dependent gene expression and have been linked to the risk of a variety of cancers including breast cancer (BC). Most BC risk variants had been identified in women of European and Asian ancestry, but genetic data for Hispanic women are scarce. Here, we investigate the association between six variants in miR binding sites and BC risk in Colombian women. Methods: We genotyped miR binding site variants in the BMPR1B, TGFBR1, IQGAP1, KRAS, SETD8 and RYR3 genes in 1022 BC cases and 1023 controls from the Colombian breast cancer case–control (Col-BCCC) study using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Multiple logistic regression and permutation techniques were applied to assess the association between genetic variants and BC risk. Results: We found no evidence of association between any of the six miR binding site variants and overall or estrogen receptor subtype-specific BC risk in Colombian women. Conclusion: Our findings may point to ethnic differences in the association between genetic variability in miR binding sites and breast cancer risk.

Introduction: Ancient DNA (aDNA)studies can support hypotheses regarding ancient populations; molecular studies can analyze the local population’s genetic composition, minimizing biases introduced by later migrations, demographic expansions, mutations, and bottleneck effects. These analyses must be performed with special care because of the low DNA concentrations and contamination risk; therefore, it is necessary to establish protocols to guarantee the reproducibility and veracity of results. Objective: The present study aims to establish a protocol to obtain ancient DNA from 16 pre-Columbian bone samples found in an excavation performed in the area «Candelaria La Nueva» in Bogota, Colombia, dated in the period «Muisca Tardio». Methods: Four founder mitochondrial DNA Amerindian haplotypes were analyzed by high resolution restriction enzyme analyses, obtaining fragments between 121 and 186 base pairs (bp). Different analyses were performed following a strict control of authenticity criteria regarding laboratory conditions, including: positive and negative controls, reproducibility of results, and verification of particular characteristics present in ancient DNA. Results: Results obtained from the bone samples showed the exclusive presence of haplogroup A in the population studied. This data support the statement of the archaeologists of a single biological population in space and time. The distribution of this haplogroup in a 100% frequency supports the hypothesis of Chibcha genetic affiliation. Conclusion: The present study is a contribution to the study of genetic diversity in archaic American populations, allowing the integration of geographic and historic data with genetic characterization techniques associated with linguistic, ethnographic, and glottochronology patterns. Following the protocol proposed in the present study allows fulfilling authenticity criteria for ancient samples with the available techniques.

Background: Genetic insights from diverse populations are key to advancing cancer detection, treatment, and prevention. Unlike other Latin American countries, Colombia lacks a centralized registry for germline and somatic mutations in breast and ovarian cancer. This study describes the country’s first national variant registry, and the occurrence of recurrent mutations and potential founder effects in Colombia. Methods: To address this gap, we implemented the first capturing protocol using the REDCap system. In a group of 213 breast and/or ovarian cancer patients harboring genetic mutations, we collected genetic, clinical, and demographic data from 13 regional centers across Colombia. Statistical analyses assessed variant distribution and patient demographics. Results: Among 229 identified variants (105 germline, 124 somatic), most were classified as pathogenic or likely pathogenic (72.4% germline, 87% somatic). BRCA1 and BRCA2 accounted for the majority of recurrent mutations. Germline recurrent variants (seen >3 times) were recorded for BRCA1 (77.7%; 21/27) and BRCA2 (22.3%; 6/27). Similarly, recurrent somatic variants were identified for BRCA1 (82.6%; 38/46) and BRCA2 (17.4%; 8/46). Notably, four recurrent variants were previously reported as founder mutations: BRCA1 c.1674del (14.3% germline and 23.7% somatic), BRCA1 c.3331_3334del (33.3% germline and 52.6% somatic), BRCA1 c.5123C>A (52.4% germline and 23.7% somatic), and BRCA2 c.2808_2811del (50% germline and 50% somatic). Most cases originated from the Andean region, highlighting regional disparities. Conclusions: This registry offers the first overview of genetic variants in Colombian breast and ovarian cancer patients. Recurrent and region-specific mutations highlight the need for population-focused data to guide targeted screening and personalized care strategies.

Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.