Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population

Cancer Med. 2023 Apr;12(7):7808-7814. doi: 10.1002/cam4.5541. Epub 2022 Dec 16.


Objective: Dihydropyrimidine dehydrogenase (DPYD) genotype is closely associated with fluoropyrimidine (FP)-induced toxicities in Caucasian population and European Medicines Agency now recommends DPYD genotype-based FP dosing strategy.

Patients and methods: The current study aimed to investigate their impact on FP-related toxicities in an Asian population using genome-wide association study (GWAS) data set from 1364 patients with colon cancer.

Results: Among 82 variants registered in the Clinical Pharmacogenetics Implementation Consortium, 74 DPYD variants were directly genotyped in GWAS cohort; however, only 7 nonsynonymous DPYD variants (CPIC variants) were identified and none of the four recurrent DPYD variants (DPYD*2A, c.2846A>T, c.1679T>G, c.1236G>A) were included. Seven CPIC variants were investigated for their association with the incidence of FP-related toxicities; however, none of these variants revealed a significant correlation with FP-related toxicities.

Conclusion: These data suggested that the DPYD genotype registered in CPIC plays a minor role in FP-related toxicities in an Asian population.

Keywords: DPYD; Asian population; fluoropyrimidine; genotyping; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects
  • Capecitabine
  • Dihydrouracil Dehydrogenase (NADP)* / genetics
  • Fluorouracil* / adverse effects
  • Genome-Wide Association Study
  • Genotype
  • Humans


  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil
  • Antimetabolites, Antineoplastic
  • Capecitabine