喀麦隆乳腺癌患者中BRCA1和BRCA2突变的特征分析：为弥合非洲基因组差距所做的努力

Background: There are profound global inequities cancer genomics research, with publications focusing on cancer genetics from Africa representing only 0.016% of the global total. This genomic underrepresentation creates significant barriers to equitable cancer care and precision medicine for African populations. BRCA1/2 mutations remain critically understudied in these communities, limiting our understanding of hereditary breast cancer patterns. This pioneering study characterizes BRCA1/2 mutations among Cameroonian patients to lay the foundation for future genomic research and address critical knowledge gaps. Methods: This hospital-based study recruited 82 breast cancer patients from 2 major treatment centers in Cameroon, an underserved population with limited access to genetic services. Following pre-test genetic counseling, saliva samples were collected and analyzed using next-generation sequencing for 29 cancer-associated genes. AI was used to improve the clarity of the language of this abstract. Results: Pathogenic mutations were identified in 23 patients (28%), with BRCA1 (15) and BRCA2 (2) accounting for 73.9% of all mutations (18.3% and 2.4% of the total population, respectively). The most frequent BRCA1 mutation was c.4484G>T(p.Arg1495Met) , present in 7 patients (46.7% of BRCA1 mutations, 8.5% of total population), followed by c.5155dup(p.Val1719Glyfs6) in 3 (including 1 with bilateral breast cancer) patients (20% of BRCA1 mutations) . BRCA2 mutations included c.1813dup(p.Ile605Asnfs 11) and c.5572del(p.Thr1858Glnfs*5) . Family history of cancer was reported in 73.9% of mutation carriers compared to 62.2% overall. Variants of uncertain significance were detected in 25.6% of patients. Two of those with the c.4484G>T BRCA1 mutation had an associated VUS in the PALB2 gene (c.365A>G(p.Asp122Gly)) . They were both under 30 and had at least 4 first- and second-degree relatives with breast and ovarian cancer. Two other patients had the same VUS in APC (c.3760A>G(p.Ile1254Val) ), all with at least 2 relatives with cancer and 1 had the BRCA1 c.4484G>T mutation and the other had no pathologic mutation identified. Conclusions: This pioneering study reveals striking cancer health disparities, with BRCA1/BRCA2 mutation frequencies exceeding rates in well-studied populations. The predominance of specific mutations and VUSs suggests population-specific genetic architecture requiring tailored approaches. Our work provides a foundation for developing culturally-appropriate cancer prevention strategies, reducing genetic testing disparities, and advancing precision medicine accessibility in vulnerable populations, ultimately contributing to the global effort to eliminate cancer health disparities.