DPYDgenetic polymorphisms in non-European patients with severe fluoropyrimidine-related toxicity: A systematic review

Abstract

BackgroundPre-treatmentDPYDscreening is mandated in the UK and EU to reduce the risk of severe and potentially fatal fluoropyrimidine-related toxicity. FourDPYDgene variants which are more prominently found in Europeans are tested.MethodsOur systematic review in patients of non-European ancestry followed PRISMA guidelines to identify relevant articles up to April 2023. Publishedin silicofunctional predictions andin vitrofunctional data were also extracted. We also undertookin silicoprediction for allDPYDvariants identified.ResultsIn 32 studies, published between 1998 and 2022, 53DPYDvariants 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 EuropeanDPYDvariants, 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.ConclusionExtending UK pre-treatmentDPYDscreening 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.