DPYD gene polymorphisms in patients with gastrointestinal tumors receiving chemotherapy with 5-fluorouracil.

Abstract

90 Background: Complete or partial deficiency of the DPD enzyme due to genetic polymorphisms of the DPYD gene causes acute toxicity of fluoropyrimidines, which are widely used in combination chemotherapy regimens for various malignant neoplasms. The purpose of the study: to identify polymorphisms of the DPYD gene significant for 5-fluorouracil-induced toxicity. Methods: Venous blood samples from Caucasian patients were used to identify alleles of *2А rs3918290, 5* rs1801159, *13 rs55886062 and rs67376798 DPYD by RT-PCR and direct sequencing. Inclusion criteria were: verified diagnosis of gastrointestinal tumors, age>18 years old, fluoropyrimidine-containing regimes of treatment. Results: 104 pts were included, 54% were female. Mean age-61 years. Colorectal cancer was found in 80.7% pts, non-colorectal in 19.3% pts. Hematological and non-hematological toxicity Gd.3-4 was found in 24% pts. Allele * 5rs18011595, which causes enzyme deficiency was found in 28% of patients, (frequency was 0.281) which is significantly higher than the population frequency of the allele charactering for Caucasoid population (p <0.05). Meanwhile genotyping did not reveal the *2A, *13 alleles and rs67376798 alleles in the DPYD gene. Conclusions: *5rs1801159 allele was found as the main DPYD polymorphism associated with fluoropyrimidine toxicity in Caucasian pts with gastrointestinal tumors.