Pharmacogenomics and Personalized Medicine (Dec 2021)
Ethnic Diversity of DPD Activity and the DPYD Gene: Review of the Literature
Abstract
Cassandra White,1,2 Rodney J Scott,1– 3 Christine Paul,1,2 Andrew Ziolkowski,3 David Mossman,3 Stephen Ackland1,2,4 1University of Newcastle, Newcastle, NSW, Australia; 2Hunter Cancer Research Alliance, Hunter Medical Research Institute, Newcastle, NSW, Australia; 3Division of Molecular Medicine, Pathology North John Hunter Hospital, Newcastle, NSW, Australia; 4Hunter Cancer Centre, Lake Macquarie Private Hospital, Gateshead, NSW, AustraliaCorrespondence: Cassandra WhiteHunter Medical Research Institute, Lot 1, Kookaburra Circuit, New Lambton Heights, NSW 2305, AustraliaTel +61 2 4042 0000Email [email protected]: Pharmacogenomic screening can identify patients with gene variants that predispose them to the development of severe toxicity from fluoropyrimidine (FP) chemotherapy. Deficiency of the critical metabolic enzyme dihydropyrimidine dehydrogenase (DPD) leads to excessive toxicity on exposure to fluoropyrimidine chemotherapy. This can result in hospitalisation, intensive care admissions and even death. Upfront screening of the gene that encodes for DPD (DPYD) has recently been implemented in regions throughout Europe and the United Kingdom. Current screening evaluates DPYD variants that are well described within Caucasian patient populations and provides genotyped-guided dose adjustment recommendations based upon the presence of these variants. This article reviews the differences in DPYD gene variants within non-Caucasian populations compared to Caucasian populations, with regard to the implications for clinical tolerance of fluoropyrimidine chemotherapies and genotype guided dose adjustment guidelines.Keywords: pharmacogenomics, non-Caucasian, DPYD gene, dihydropyrimidine dehydrogenase
