Table 2_Precision medicine on a budget in Africa: using existing genetic data to mitigate adverse drug reactions to conventional cancer drugs.xlsx

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.

药物代谢酶与转运蛋白的基因变异与药物不良反应（adverse drug reactions, ADRs）密切相关。受环境与遗传差异影响，不同人群对癌症药物的不良反应表现存在显著异质性。由于药物开发需投入大量资源且成本高昂，非洲国家普遍依赖基于非非洲遗传背景研发的癌症药物。非洲黑人人群的药物不良反应负担较重，部分原因在于临床使用的药物未针对该人群进行优化。尽管非洲黑人是遗传多样性最高的人群，却是目前研究程度最低的群体。当前针对非洲黑人人群的药物遗传学研究（pharmacogenetic studies）极度匮乏，因此亟需开展该人群的药物基因组学研究（pharmacogenomic studies），以优化给药方案并最大限度降低药物不良反应风险。
本研究选取卡培他滨（capecitabine）与环磷酰胺（cyclophosphamide）两种临床常用的通用癌症药物，依托PharmGKB平台及多个基因组数据库，论证了在非洲地区开展药物基因组学研究的必要性。我们采用的计算分析方法，可识别出相较于其他族群，在非洲黑人人群中富集或缺失的、既往已报道及未报道的与药物毒性及疗效相关的基因变异。上述研究结果提示，卡培他滨与环磷酰胺可能无法在非洲黑人人群中发挥最优治疗效果，或会增加该人群发生药物不良反应的概率。这一发现凸显了开展基于人群的药物筛选与药物开发的紧迫性，以最大限度降低药物不良反应并保障更优的临床治疗结局。
鉴于当前全球基因组研究中非洲黑人人群的样本占比严重不足，非洲地区科研人员可借鉴本研究的低成本分析方案，评估现有药物用于疾病治疗的适用性。但从长远发展来看，非洲科研人员需启动大规模本土化基因组研究，以推动适配非洲人群的创新药物研发，并促进精准医学在非洲大陆的落地推广。