Dpyd, encoding dihydropyrimidine dehydrogenase (DPD), is a key gene in fluoropyrimidine metabolism. DPD is the rate-limiting enzyme for the breakdown of fluoropyrimidines like 5-fluorouracil and capecitabine, which are widely used antineoplastic drugs [4,5].

Prospective Dpyd genotyping in cancer patients starting fluoropyrimidine-based therapy is feasible in routine clinical practice. Genetic variants in Dpyd, such as Dpyd*2A, c.2846A>T, c.1679T>G, and c.1236G>A, are associated with reduced DPD activity, leading to increased fluoropyrimidine-related severe toxicity. Genotype-guided dose reductions improve patient safety. For instance, Dpyd*2A and c.1679T>G carriers benefit from a 50% initial dose reduction, while the optimal dose reduction for c.1236G>A and c.2846A>T carriers may need further investigation [1]. Also, Dpyd-guided fluoropyrimidine dosing does not negatively affect progression-free survival (PFS) and overall survival (OS) in pooled Dpyd variant carriers, though close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G>A carriers [2]. Additionally, Dpyd exon 4 deletion and copy number variation (CNV) in Dpyd may contribute to Dpyd-mediated fluoropyrimidine toxicity [3].

In conclusion, Dpyd is crucial for fluoropyrimidine metabolism. Understanding Dpyd genetic variants through genotyping helps in individualizing fluoropyrimidine therapy, improving patient safety, and potentially treatment outcomes in cancer patients receiving these drugs. Research on Dpyd continues to explore the impact of various genetic changes on drug response and toxicity, which is essential for optimizing cancer treatment.