SO-29 Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: Prevalence and correlation between DPYD-genotype mutations and P-uracil concentrations

Fluoropyrimidines (FP) are the cornerstone of chemotherapy several, mainly gastrointestinal, solid tumors. FP includes 5-fluorouracil, capecitabine, and tegafur, all metabolized by dihydropyrimidine dehydrogenase (DPD) enzyme. Patients with decreased DPD-activity have a higher risk getting severe toxicity if treated standard doses. The is currently test in Denmark DPYD-genotype-test and/or measurement endogenous compound uracil (DPD-phenotype test). In Denmark, recommended starting dose for patients diagnosed partial DPD-deficiency 50%. treatment contraindicated complete due to high life-threatening adverse effects. one variant SNP concentrations above 16 ng/ml categorized as having DPD deficiency. However, deficiency they homozygous or heterozygous (patients with≥ 2 different SNPs) 150 ng/ml. France Netherlands, prevalence clinically relevant DPYD variants was 4.7% 7.7% respectively. No studies reported data on P-uracil Danish cancer patients. We collected from public hospital laboratories performing DPYD-genotype DPD-phenotype analysis 1st July 2020 31st December 2021. were genotyped four DPYD-variants: rs3918290, rs67376798, rs55886062, rs56038477/rs75018182. Most samples using LAMP (loop-mediated isothermal amplification) technology (Lc-Dpd4mut-Lp-24-Lacar Mdx Technologies). Plasma measured liquid chromatography-mass spectrometry (LC-MS). total 4228 tested. 1985 only tested method (P-uracil=17, DPYD-genotype=1968). 2243 DPYD-genotyping. Of 4215 DPYD-genotyped patients, 3895 (92.4%) wild type 316 (7.5%) (SNP'S). rs3918290 (1%, n=43), rs67376798 (1.4%, n=57), rs55886062 (0.2%, n=8) rs56038477/rs75018182 (4.9%, n=208). Four (0.1%) heterozygous. Among 2260 tested, 2132 (94.3%) had an concentration below remaining 128 (5.7%) ≥ ng/mL < values found. Median 8 (range 5-82 ng/ml). Both geno- phenotype available Uracil among lower (mean 8.6 ng/ml) compared DPYD-variants 11.2 ng/ml), mean difference 2.7 (95% CI; 1.9-3.4 4.8% (n=99) 16.8% (n=29) group DPYD-mutations. DPYD-mutations 7.6% line results similar other European populations. 5.7% phenotyped type, but varied substantially both groups. Data regarding events needed conclude clinical implications.