DPYD, which encodes dihydropyrimidine dehydrogenase (DPD), is a crucial gene. DPD is the rate-limiting enzyme for the metabolism of fluoropyrimidines like 5-fluorouracil and capecitabine. Its function in this metabolic pathway is essential for the proper breakdown of these anticancer drugs, thus influencing their efficacy and toxicity in cancer treatment [4,5].

Fluoropyrimidine treatment can lead to severe toxicity in up to 30% of patients, often due to reduced DPD activity caused by genetic variants in DPYD. Prospective screening for four relevant DPYD variants (DPYD*2A [rs3918290, c.1905 + 1G>A, IVS14 + 1G>A], c.2846A>T [rs67376798, D949V], c.1679T>G [rs55886062, DPYD*13, I560S], and c.1236G>A [rs56038477, E412E, in haplotype B3]) in Dutch cancer patients showed that DPYD genotype-guided dose individualisation improved patient safety. DPYD variant carriers had a higher frequency of severe fluoropyrimidine-related toxicity compared to wild-type patients. For DPYD*2A and c.1679T>G carriers, a 50% initial dose reduction was adequate, while for c.1236G>A and c.2846A>T carriers, a larger dose reduction might be needed [1]. In a matched-pair analysis, DPYD-guided fluoropyrimidine dosing did not negatively affect progression-free survival (PFS) and overall survival (OS) in pooled DPYD variant carriers, though c.1236G>A carriers had a shorter PFS [2]. A study in Canadian patients also found that a DPYD exon 4 deletion was associated with fluoropyrimidine toxicity, suggesting that copy number variation in DPYD may be an underappreciated determinant of toxicity [3].

In conclusion, DPYD is essential for the metabolism of fluoropyrimidines. Research on DPYD-related genetic variants through patient-based studies has shown its significance in guiding fluoropyrimidine-based cancer treatment. Understanding DPYD gene function and its variants helps in improving the safety and efficacy of fluoropyrimidine therapy for cancer patients.