Background: Pre-treatment DPYD screening is mandated in the UK and EU to reduce the risk of severe and potentially fatal fluoropyrimidine-related toxicity. Four DPYD gene variants which are more prominently found in Europeans are tested. Methods: Our systematic review in patients of non-European ancestry followed PRISMA guidelines to identify relevant articles up to April 2023. Published in silico functional predictions and in vitro functional data were also extracted. We also undertook in silico prediction for all DPYD variants identified. Results: In 32 studies, published between 1998 and 2022, 53 DPYD variants were evaluated in patients from 12 countries encompassing 5 ethnic groups: African American, East Asian, Latin American, Middle Eastern, and South Asian. One of the 4 common European DPYD variants, c.1905+1G>A, is also present in South Asian, East Asian and Middle Eastern patients with severe fluoropyrimidine-related toxicity. There seems to be relatively strong evidence for the c.557A>G variant, which is found in individuals of African ancestry, but is not currently included in the UK genotyping panel. Conclusion: Extending UK pre-treatment DPYD screening to include variants that are present in some non-European ancestry groups will improve patient safety and reduce race and health inequalities in ethnically diverse societies.

MP has received partnership funding for the following: MRC Clinical Pharmacology Training Scheme (co-funded by MRC and Roche, UCB, Eli Lilly and Novartis). He has developed an HLA genotyping panel with MC Diagnostics, but does not benefit financially from this. He is part of the IMI Consortium ARDAT (www.ardat.org). None of the funding MP received is related to the current paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This work was supported by the NHS Race & Health Observatory.

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Data used in this review is provided in Supplementary Appendices; any additional data are available upon request to the corresponding author.