Djomkam Zune Alexandra Lindsey, Olwal Charles Ochieng', Agbeli Emmanuel, Diallo Abdoulaye Baniré, Amoako Emmanuella, Bediako Yaw, Paemka Lily
Yemaachi Biotech, Accra, Ghana.
West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
Front Bioinform. 2025 Aug 14;5:1555637. doi: 10.3389/fbinf.2025.1555637. eCollection 2025.
Variations in drug-metabolizing enzymes and transporters are associated with adverse drug reactions (ADRs). ADRs to cancer drugs can differ among populations owing to environmental and genetic differences. Due to limited resources and prohibitive costs associated with drug development, African countries rely on cancer drugs developed from non-African genetic backgrounds. Black Africans carry a high burden of ADRs partly because of the use of poorly optimized drugs. Black Africans are the least studied population despite being the most genetically diverse. There is a profound lack of pharmacogenetic studies in Black African populations, necessitating an urgent need for pharmacogenomic studies in Black African populations to optimize dosing and minimize ADRs. Using two common generic cancer drugs, capecitabine and cyclophosphamide, we leveraged the PharmGKB platform and several genomic databases to highlight the need for pharmacogenomic studies in Africa. Our computational approach identifies previously reported and unreported toxicity- and efficacy-associated variants that are overrepresented or underrepresented in Black Africans relative to other ethnicities. These findings suggest that capecitabine and cyclophosphamide may not work optimally and/or may predispose Black Africans to ADRs. This underscores the need for population-based drug screening and development to minimize ADRs and guarantee better treatment outcomes. Since Black Africans are currently underrepresented in genomic studies, African scientists could adopt our low-cost approach to evaluate the suitability of existing drugs for treating diseases. However, in the long term, African scientists must initiate large-scale genomic studies that will drive the discovery of African-tailored drugs and promote the implementation of precision medicine on the continent.
药物代谢酶和转运蛋白的变异与药物不良反应（ADR）相关。由于环境和遗传差异，不同人群对癌症药物的不良反应可能有所不同。由于药物开发资源有限且成本高昂，非洲国家依赖于基于非非洲遗传背景开发的癌症药物。非洲黑人承受着较高的药物不良反应负担，部分原因是使用了优化不佳的药物。尽管非洲黑人的基因多样性最高，但却是研究最少的人群。非洲黑人人群中严重缺乏药物遗传学研究，因此迫切需要在非洲黑人人群中开展药物基因组学研究，以优化给药剂量并减少药物不良反应。我们使用两种常见的通用癌症药物——卡培他滨和环磷酰胺，利用药物基因组学知识库（PharmGKB）平台和多个基因组数据库，强调了在非洲开展药物基因组学研究的必要性。我们的计算方法识别出了先前已报道和未报道的与毒性和疗效相关的变异，这些变异在非洲黑人中相对于其他种族而言要么过度表达，要么表达不足。这些发现表明，卡培他滨和环磷酰胺可能无法达到最佳疗效，和/或可能使非洲黑人更容易出现药物不良反应。这凸显了开展基于人群的药物筛选和开发以减少药物不良反应并确保更好治疗效果的必要性。由于目前非洲黑人在基因组研究中的代表性不足，非洲科学家可以采用我们的低成本方法来评估现有药物治疗疾病的适用性。然而，从长远来看，非洲科学家必须启动大规模的基因组研究，以推动发现适合非洲人的药物，并促进在非洲大陆实施精准医学。
