Abstract 23: Pharmacogenomics of Breast, Cervical and Prostate Cancers: Cytochrome P450 Variants and Implications for Chemotherapy in African Populations

Abstract Purpose: By 2040, Africa is projected to bear the highest global burden of cancer. Chemotherapy remains a mainstay of treatment, yet patient responses vary significantly due to genetic mutations, particularly in coding for Cytochrome P450(CYP) enzymes. This study investigates the prevalence and implications of CYP gene variants on chemotherapeutic drug metabolism in three common cancers in Africa comparing African and European populations, thus highlighting the pharmacogenomic factors contributing to these differences. Methods: Pharmacogenomic single nucleotide polymorphisms (pharmaSNPs) specific to CYP variants were identified from the Pharmacogenomic Knowledgebase (PharmGKB, www.pharmgkb.org) and analyzed using the LDlink genome browser. Data were analysed using R to compare allele frequencies across populations of African, as well as European descent with 95% confidence intervals. Allele-specific ratios were calculated using the LDhap tool from the National Cancer Institute, Division of Cancer Epidemiology and Genetics. Results: Sample sizes included 661 participants from Europe and 710 from Africa. The CYP2B6 allele, commonly associated with decreased enzyme activity, was significantly more prevalent in African populations (46.9% in a Ghanaian cohort and 32.8% in African Americans) compared to Asians (18.0%) and Caucasians (25.6%). Patients with the CYP2B6 variant exhibited a prolonged circulating half-life of cyclophosphamide, correlating with worse overall survival outcomes. Conclusion: This study underscores the need for comprehensive genomic research on African populations to address disparities in cancer treatment outcomes. Given the rising incidence of cancer driven by increased carcinogen exposure, poor diet, and physical inactivity, understanding CYP2B6 pharmacogenetics is necessary for optimizing chemotherapeutic strategies in Africa. Incorporating pharmacogenomic insights into clinical practice will be critical for improving survival rates and tailoring cancer therapies to diverse populations. Citation Format: Sophia Okeke, Chiamaka Offorbuike, Boluwatife Adewale, Ehis Aigbonoga, Ighodalo Aito, Oluwaferanmi Alufa, Olusola Agbana, Kehinde Arokoyo, Tolulope Onakoya, James Chibor. Pharmacogenomics of Breast, Cervical and Prostate Cancers: Cytochrome P450 Variants and Implications for Chemotherapy in African Populations [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 23.