Pharmacogenomics in Cancer Treatment: Challenges and Opportunities in African Settings

BACKGROUND: Cancer incidence in Africa is projected to reach 2.1 million new cases annually by 2040. Current treatment guidelines remain largely based on pharmacogenomic data predominantly from European and Asian genetic profiles, potentially compromising safety and efficacy in African patients. However, limited clinical validation data, extreme intra-population genetic diversity, and significant healthcare infrastructure barriers constrain the translational application of pharmacogenomics in Africa. OBJECTIVE: This review critically examines pharmacogenomic variants with established clinical actionability in cancer treatment, focusing on those with differential frequencies or African-specific alleles, and evaluates the evidence base for their implementation in African healthcare settings. METHODS: We searched PubMed/MEDLINE, PharmGKB, dbSNP, and Google Scholar for peer-reviewed studies reporting pharmacogenomic variants in African or African-ancestry populations relevant to cancer therapeutics. We synthesised evidence from recent African and global studies on pharmacogenomic variants affecting commonly used chemotherapy agents. RESULTS: Several variants show marked frequency differences between African-ancestry reference populations and European populations, including DPYD rs115232898 (2.06% vs. 0.00%), CYP2D6*17 (18.76% vs. 0%), and CYP3A5*6 (12.82% vs. 0%). However, many of these estimates derive primarily from African-American datasets and should not be interpreted as representative of continental African populations. African-specific variants such as CYP2D6*17 and DPYD rs115232898 are underrepresented in guideline development datasets. Intra-African genetic diversity is the highest globally, with Khoi-San populations harbouring extensive private variation, suggesting that no single pharmacogenomic panel will be universally applicable across the continent. CONCLUSION: While pharmacogenomics holds substantial promise for personalising cancer treatment in Africa, its current translational readiness is limited by a critical lack of African-specific clinical validation data. Priorities include multi-site validation studies, development of African-enriched genotyping panels, and integration of pharmacogenomic education into oncology practice. Implementation must be accompanied by ethical frameworks ensuring data sovereignty and equitable benefit-sharing.