Afolabi Boluwatife Lawrence, Mazhindu Tinashe, Zedias Chikwambi, Borok Margaret, Ndlovu Ntokozo, Masimirembwa Collen
African Institute of Biomedical Science and Technology, Harare P.O. Box 2294, Zimbabwe.
Department of Biotechnology, School of Health Sciences, Chinhoyi University of Technology, Chinhoyi Private Bag 7724, Zimbabwe.
J Pers Med. 2023 Mar 28;13(4):588. doi: 10.3390/jpm13040588.
Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on dihydropyrimidine dehydrogenase () genetic polymorphism and have been shown to reduce these AEs in patients of European ancestry. This study aimed to evaluate, for the first time, the clinical applicability of these guidelines in a cohort of cancer patients on fluoropyrimidine standard of care treatment in Zimbabwe. DNA was extracted from whole blood and used for genotyping. Adverse events were monitored for six months using the Common Terminology Criteria for AEs (CTCAE) v.5.0. None of the 150 genotyped patients was a carrier of any of the pathogenic variants (*2A, *13, rs67376798, or rs75017182). However, severe AEs were high (36%) compared to those reported in the literature from other populations. There was a statistically significant association between BSA ( = 0.0074) and BMI ( = 0.0001) with severe global AEs. This study has shown the absence of the currently known actionable variants in the Zimbabwean cancer patient cohort. Therefore, the current pathogenic variants in the guidelines might not be feasible for all populations hence the call for modification of the current guidelines to include minority populations for the benefit of all diverse patients.
氟嘧啶常用于治疗结直肠癌。然而，它们与不良事件（AE）相关，其中胃肠道、骨髓抑制和手足红斑性感觉异常最为常见。临床指南根据二氢嘧啶脱氢酶（DPD）基因多态性来确定氟嘧啶的剂量，并且已证明这可减少欧洲血统患者的这些不良事件。本研究旨在首次评估这些指南在津巴布韦接受氟嘧啶标准治疗的癌症患者队列中的临床适用性。从全血中提取DNA并用于DPD基因分型。使用不良事件通用术语标准（CTCAE）v.5.0对不良事件进行了六个月的监测。在150名进行基因分型的患者中，没有一人是任何致病变体（*2A、*13、rs67376798或rs75017182）的携带者。然而，与其他人群文献报道的相比，严重不良事件发生率较高（36%）。体表面积（BSA，P = 0.0074）和体重指数（BMI，P = 0.0001）与严重的整体不良事件之间存在统计学上的显著关联。本研究表明，在津巴布韦癌症患者队列中不存在目前已知的可采取行动的DPD变体。因此，指南中目前的致病变体可能并非对所有人群都可行，因此呼吁修改当前指南以纳入少数族裔人群，从而使所有不同患者受益。
