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 germline pharmacogenomic variants associated with cancer therapeutics obtained from the Clinical Pharmacogenetics (ClinPGx) database were retrieved from the Phase 3 1,000 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 (1KGP) (the Yoruba (n = 108) and Esan (n = 99) tribes). The study included pharmacogenetic variants with Level 1 A evidence CYP2D64 (Tamoxifen), CYP3A53, 6, 7 (Tacrolimus), DPYD rs115232898, rs17376848, rs1801159, rs1801265 (5-Fluorouracil and Capecitabine), and TPMT3C (Thiopurines: 6-MP, Azathioprine). Hardy–Weinberg equilibrium (HWE) was calculated, and a cross-population comparative analysis was conducted between Nigerian populations and global reference populations from Europe (British), East Asia (Han Chinese), and the Americas (Peruvians). Results Among the Esan and Yoruba populations in Nigeria, CYP2D6 poor metabolizer phenotypes (defined by two non-functional diplotypes according to CPIC) were infrequent and observed for CYP2D64 at a frequency of 1.0% (95% CI: 0.2–5.5) in the Esan population, while absent in the Yoruba population, with potential implications for reduced tamoxifen efficacy. Homozygosity for non-functional CYP3A5 alleles (3, 6, and 7), indicating complete loss of CYP3A5 expression and corresponding to poor tacrolimus metabolizer status, was identified in approximately 3% of the Esan population and nearly twice that proportion in the Yoruba population. The minor allele frequency of DPYD rs115232898, associated with decreased fluorouracil metabolism, differed between populations, occurring at 1.0% (95% CI: 0.3–3.6) in Esan and 4.2% (95% CI: 2.2–7.7) in Yoruba individuals. For TPMT3C, non-functional diplotypes were not observed in the Esan population, whereas a low frequency (0.9%) was detected among Yoruba individuals. Global comparisons showed marked population specificity: CYP3A56 and *7 nonfunctional alleles were enriched in Nigerians compared to British, Peruvians and Han Chinese populations. The decreased function DPYD rs115232898 allele was observed at a frequency of 3% among Nigerians and was absent in all 3 global populations examined. Within Nigeria, its frequency was approximately 4 times higher in the Yoruba population (Esan: 1%, Yoruba: 4%). 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.

Clinically actionable pharmacogenomic variants for anticancer therapy in Nigeria: first comprehensive variant profiling in underrepresented Nigerian cohorts

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2026年2月9日

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Michael Pius Ukpe,
Anastecia Chinasa Ezeanuka

摘要

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 germline pharmacogenomic variants associated with cancer therapeutics obtained from the Clinical Pharmacogenetics (ClinPGx) database were retrieved from the Phase 3 1,000 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 (1KGP) (the Yoruba (n = 108) and Esan (n = 99) tribes). The study included pharmacogenetic variants with Level 1 A evidence CYP2D6*4 (Tamoxifen), CYP3A5*3, *6, *7 (Tacrolimus), DPYD rs115232898, rs17376848, rs1801159, rs1801265 (5-Fluorouracil and Capecitabine), and TPMT*3C (Thiopurines: 6-MP, Azathioprine). Hardy–Weinberg equilibrium (HWE) was calculated, and a cross-population comparative analysis was conducted between Nigerian populations and global reference populations from Europe (British), East Asia (Han Chinese), and the Americas (Peruvians).

Results

Among the Esan and Yoruba populations in Nigeria, CYP2D6 poor metabolizer phenotypes (defined by two non-functional diplotypes according to CPIC) were infrequent and observed for CYP2D6*4 at a frequency of 1.0% (95% CI: 0.2–5.5) in the Esan population, while absent in the Yoruba population, with potential implications for reduced tamoxifen efficacy. Homozygosity for non-functional CYP3A5 alleles (*3, *6, and 7), indicating complete loss of CYP3A5 expression and corresponding to poor tacrolimus metabolizer status, was identified in approximately 3% of the Esan population and nearly twice that proportion in the Yoruba population. The minor allele frequency of DPYD rs115232898, associated with decreased fluorouracil metabolism, differed between populations, occurring at 1.0% (95% CI: 0.3–3.6) in Esan and 4.2% (95% CI: 2.2–7.7) in Yoruba individuals. For TPMT*3C, non-functional diplotypes were not observed in the Esan population, whereas a low frequency (0.9%) was detected among Yoruba individuals. Global comparisons showed marked population specificity: CYP3A5*6 and *7 nonfunctional alleles were enriched in Nigerians compared to British, Peruvians and Han Chinese populations. The decreased function DPYD rs115232898 allele was observed at a frequency of 3% among Nigerians and was absent in all 3 global populations examined. Within Nigeria, its frequency was approximately 4 times higher in the Yoruba population (Esan: 1%, Yoruba: 4%).

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.