Clinical and pharmacogenetic importance of the DPYD gene in the treatment of fluoropyrimidines in clinical oncology
Clinical and pharmacogenetic importance of the DPYD gene in the treatment of fluoropyrimidines in clinical oncology
Keywords:
fluorouracil, capecitabine, pharmacogenetics, chemotherapyAbstract
Introduction: Fluoropyrimidines (5-fluorouracil/capecitabine) are fundamental chemotherapeutic agents in oncology. The dihydropyrimidine dehydrogenase (DPD) enzyme, encoded by the DPYD gene, metabolizes 80–85% of the drug. Variants in DPYD reduce enzymatic activity, leading to toxic drug accumulation, severe toxicity (occurring in 10–40% of patients), and fatal outcomes in 1% of cases. Objective: To summarise the current scientific evidence on the clinical relevance of DPYD genotyping, with a view to optimising the safety and efficacy of chemotherapeutic treatment. Methodology: A literature review was conducted in accordance with PRISMA principles. Databases including PharmGKB, PubMed, and ScienceDirect were searched using terms such as "fluorouracil," "capecitabine," "pharmacogenetics," and "DPYD." The study incorporated open-access articles in English and Spanish published between 2020 and 2025. Please note that letters to the editor, abstracts and paywalled publications were excluded from the study. Results: Four critical variants were identified (c.1905+1G>A, c.1679T>G, c.2846A>T, and c.1236G>A/HapB3) associated with an increased risk of neutropenia, mucositis, severe diarrhea, and mortality. Preventive genotyping allows for patient classification based on metabolic phenotype and initial dose adjustments ranging from 25% to 50%. Discussion: The implementation of DPYD genotyping has been shown to effectively reduce the incidence of severe toxicity, thereby improving the safety profile. However, its clinical adoption remains inconsistent, with significant limitations in developing countries due to a lack of specialised infrastructure, clinical awareness, and pharmacogenomic policies. Conclusions: DPYD pharmacogenetics is crucial for the safety of fluoropyrimidine use; genotyping of key variants and dose adjustment prevent serious toxicities.
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