Background: Hereditary cancer is increasingly recognized as a major contributor to the oncology burden in Africa. Cameroon, like most sub-Saharan countries, had long lacked access to structured genetic counseling and germline testing. Through the Genetic Cancer Families (GENCAF) initiative—whose acceptability was established in a prior feasibility study and whose implementation is described separately—we conducted a systematic multigene panel sequencing of cancer patients in the country. Methods: We performed a cross-sectional analysis of 94 consecutive cancer patients enrolled in the GENCAF program between May 2022 and December 2023. All participants received standardized pre-test counseling and saliva-based DNA sampling. Sequencing was performed using a 29-gene hereditary cancer panel. Variants were classified according to American College of Medical Genetics and Genomics (ACMG) criteria. We analyzed the prevalence, spectrum, and clinical correlates of pathogenic/likely pathogenic (P/LP) variants, variants of uncertain significance (VUS), and multi-gene variant profiles across all cancer types. Results: Among 94 individuals tested (mean age 43.4 years, 95.7% women), breast cancer was the predominant diagnosis (87.2%). Germline P/LP variants were identified in 27.7% (26/94; 25 pathogenic, 1 likely pathogenic). Breast Cancer gene (BRCA) 1 accounted for 69.2% of all P/LP findings. VUS were present in 26.6% of patients across 13 genes. Eight patients (8.5%) carried co-occurring P/LP and VUS in different genes. Pathogenic variants were more common in individuals with a family history (33%) than without (16%; p = 0.12). Conclusion: This study provides a detailed genomic mapping of hereditary cancer susceptibility in Cameroon. The high prevalence of BRCA1 P/LP variants, substantial VUS burden across 13 genes, and early age at diagnosis highlight the urgency of integrating genetic counseling and testing into national cancer control strategies.
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