Characterizing BRCA Mutations in Cameroonian Breast Cancer Patients: Advancing Precision Oncology and Bridging the Genomic Gap in Sub-Saharan Africa

Abstract

Background: Breast cancer is the most commonly diagnosed malignancy worldwide and represents a growing cause of cancer mortality in sub-Saharan Africa. African populations remain underrepresented in global cancer genomics research, with publications addressing cancer genetics from Africa constituting only 0.016% of the worldwide total. Breast Cancer gene 1 (BRCA1) and BRCA2 mutations, central to hereditary breast cancer, remain understudied in sub-Saharan African populations. Building on prior work demonstrating the willingness of Cameroonian patients to undergo genetic testing and counseling, this study characterizes BRCA1 and BRCA2 mutations among Cameroonian breast cancer patients to address knowledge gaps. Methods: This prospective study recruited 82 breast cancer patients from three major oncology referral centers in Yaounde, Cameroon. Following pre-test genetic counseling, saliva samples were collected and analyzed using next-generation sequencing for a panel of 29 cancer-associated genes. Genetic variants were classified according to the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines. Statistical analysis included descriptive statistics, t-tests, chi-square tests, Fisher’s exact test, and linear regression. Results: Among 82 breast cancer patients, BRCA1 pathogenic or likely pathogenic (P/LP) variants were identified in 16 patients (19.5%) and BRCA2 in 2 patients (2.4%), giving a combined BRCA1/2 P/LP rate of 22.0%. The most frequent BRCA1 variant was c.4484G>T (p.Arg1495Met), identified in 7 patients (43.8% of BRCA1-positive patients), raising the possibility of a population-specific recurrent variant. Variants of uncertain significance (VUS) were detected in 25.6% of patients. Regression analysis identified younger age at diagnosis (p = 0.04) and positive family history (p = 0.03) as significant predictors of BRCA1/2 carrier status. Conclusions: This study reveals a high prevalence of BRCA1/2 pathogenic variants in Cameroonian breast cancer patients. The recurrence of a specific BRCA1 mutation raises the hypothesis of a population-specific genetic architecture warranting further investigation. These findings reveal the need for inclusive genomic research and equitable implementation of precision oncology in underrepresented communities.