Haplotype structure defines effects of common DPYD variants c.85T > C (rs1801265) and c.496A > G (rs2297595) on dihydropyrimidine dehydrogenase activity: Implication for 5-fluorouracil toxicity.

ABSTRACT:

Aims

The aim of this study was to identify risk variants and haplotypes that impair dihydropyrimidine dehydrogenase (DPD) activity and are, therefore, candidate risk variants for severe toxicity to 5-fluorouracil (5-FU) chemotherapy.

Methods

Plasma dihydrouracil/uracil (UH₂ /U) ratios were measured as a population marker for DPD activity in a total of 1382 subjects from 4 independent studies. Genotype and haplotype correlations with UH₂ /U ratios were assessed.

Results

Significantly lower UH₂ /U ratios (p_anova < 2 × 10^-16 ) were observed in carriers of the 4 well-studied 5-FU toxicity risk variants with mean differences (MD) of -43.7% for DPYD c.1905 + 1G > A (rs3918290), -46.0% for DPYD c.1679T > G (rs55886062),

SUBMITTER: Hamzic S 

PROVIDER: S-EPMC8359980 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature