Ethnic Diversity of DPD Activity and the DPYD Gene: Review of the Literature

Cassandra White; Rodney J Scott; Christine Paul; Andrew Ziolkowski; David Mossman; Stephen Ackland

doi:10.2147/PGPM.S337147

Ethnic Diversity of DPD Activity and the DPYD Gene: Review of the Literature

Pharmgenomics Pers Med. 2021 Dec 9:14:1603-1617. doi: 10.2147/PGPM.S337147. eCollection 2021.

Authors

Cassandra White^{1

2}, Rodney J Scott^{1

2

3}, Christine Paul^{1

2}, Andrew Ziolkowski³, David Mossman³, Stephen Ackland^{1

2

4}

Affiliations

¹ University of Newcastle, Newcastle, NSW, Australia.
² Hunter Cancer Research Alliance, Hunter Medical Research Institute, Newcastle, NSW, Australia.
³ Division of Molecular Medicine, Pathology North John Hunter Hospital, Newcastle, NSW, Australia.
⁴ Hunter Cancer Centre, Lake Macquarie Private Hospital, Gateshead, NSW, Australia.

Abstract

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: DPYD gene; dihydropyrimidine dehydrogenase; non-Caucasian; pharmacogenomics.

Publication types

Review