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Dihydropyrimidine dehydrogenase testing: From Pharmacogenomics to Equitable Practice.
Jacquelyne J Gaddy1, Pamela L Kunz1, Raghav Sundar2
1Yale Cancer Center New Haven, CT United States.
Summary
Expanded DPYD testing is crucial for identifying patients with uncommon variants that cause severe toxicities. This is especially important for patients of African ancestry, who may carry rare, highly toxic DPYD variants.
Area of Science:
- Pharmacogenomics
- Clinical Toxicology
Background:
- DPYD gene variants are associated with severe fluoropyrimidine drug toxicities.
- Current DPYD testing may not cover all clinically relevant variants, particularly in diverse populations.
Purpose of the Study:
- To highlight the need for broader DPYD genetic testing.
- To emphasize the limitations of existing DPYD screening protocols.
- To underscore the importance of considering DPYD variants in patients of African ancestry.
Main Methods:
- Commentary based on a cohort study.
- Review of current DPYD testing strategies and their limitations.
Main Results:
- Uncommon DPYD variants can lead to severe drug-induced toxicities.
- Existing DPYD testing profiles are insufficient.
- Patients of African ancestry may harbor rare, high-risk DPYD variants.
Conclusions:
- Expand DPYD testing to include a wider range of variants.
- Address limitations in current DPYD screening.
- Prioritize genetic screening for DPYD variants in all patient populations, including those of African ancestry, to mitigate severe toxicities.
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