Introduction: Sub-Saharan Africa faces a rapidly growing cancer burden, yet genetic counseling and hereditary cancer testing remain absent in most national health systems. In Cameroon, no structured oncogenetics services existed prior to 2020, despite the frequent clinical observation of early-onset cancers and strong familial clustering. This project aimed to implement and evaluate the operational outcomes of the first structured genetic counseling and multigene testing program for hereditary cancer in Cameroon. Methods: The Genetic Cancer Families (GENCAF) initiative was established as a collaborative North-South (University of Chicago, City of Hope) and South-South (University of Ibadan) program across three oncology centers in Yaounde. Following capacity building and a feasibility study whose results are published separately, the program proceeded to pilot germline testing using next-generation sequencing (NGS) for 29 cancer susceptibility genes in 94 patients. Results: The program trained Cameroon’s first two certified cancer genetic counselors and 19 supporting health professionals. The feasibility and acceptability outcomes (including knowledge-score improvement from 41% to 78%, p < 0.001) were measured in a prior cross-sectional cohort of 160 patients and are not outcomes of the present testing cohort of 94 patients. Operational sequencing of 94 probands identified pathogenic or likely pathogenic (P/LP) variants in 27.7%, with Breast Cancer gene 1 (BRCA1) being the most prevalent gene (19.1%). Additionally, 26.6% carried variants of uncertain significance (VUS). Conclusion: GENCAF demonstrates the feasibility and high acceptability of introducing oncogenetics in Cameroon. The high diagnostic yield (27.7%) confirms a substantial burden of hereditary cancer, necessitating the integration of genetic services into national cancer control plans.
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