Clinically Actionable Pharmacogenomic Variants for Anticancer Therapy in Nigeria: First Comprehensive Variant Profiling in Underrepresented Nigerian Cohorts

Background Advances in pharmacogenomic research have ushered in a new era of precision medicine in cancer care. However, evidence on the effects of pharmacogenomic variants on anticancer drug efficacy and safety in the Nigerian population is scarce. As a result, pharmacogenomic testing is not currently included in cancer care in Nigeria. This study aimed to investigate the minor allele frequencies (MAFs) and genotype distributions of all clinically validated pharmacogenomic variants associated with anticancer drugs in the Nigerian population at PharmGKB Level A1. Methods Allele counts and allele frequencies of pharmacogenes and variants associated with cancer therapeutics obtained from the Clinical Pharmacogenetics (ClinPGx) database were retrieved from the Phase 3 1000 Genomes project via the Ensembl REST API and genome browser. The primary population of interest in this study was the 207 Nigerians included in the 1000 Genomes Project (the Yoruba (n = 108) and Esan (n = 99) tribes). All variants with a minor allele frequency < 1% were excluded. Hardy–Weinberg equilibrium (HWE) was calculated, and a cross-population comparative analysis was conducted between Western populations and Nigerian populations. Results Across the Esan and Yoruba populations, CYP2D6*2 ( rs1135840) presented the highest minor allele frequency (57.3%, 95% CI: 50.4–64.2; 60.7%, 95% CI: 53.9–67.5), whereas CYP2D6*4 ( rs3892097 ) presented the lowest frequency (7.6%, 95% CI: 4.6–12.1; 5.6%, 95% CI: 3.2–9.5). Among the CYP3A5 variants, CYP3A5*1 (rs15524) exhibited the highest frequency (26.3%, 95% CI: 20.6–32.8; 27.8%, 95% CI: 22.2–34.1). DPYD (rs1801265) showed the greatest variability (42.9%, 95% CI: 36.2–49.9; 43.5%, 95% CI: 37.1–50.2), whereas TPMT*3C ( rs1142345 ) alleles were rare (4.0%, 95% CI: 2.1–7.8; 6.0%, 95% CI: 3.6–10.0). Compared with Western populations, Nigerians presented significantly higher CYP2D6*2 and CYP3A5*1 frequencies but lower CYP2D6*4 and DPYD (rs17376848) frequencies. Conclusion These population-specific patterns highlight the clinical importance of pharmacogenetic screening to guide dose optimisation and improve cancer treatment outcomes. Integrating pharmacogenomic testing into oncological care in Nigeria would enhance therapeutic efficacy, minimise adverse effects, and advance the implementation of precision medicine across African populations.