Open AccessStudy of polymorphisms of UGT1A1 and DPYD genes in chemotherapy for colorectal cancer
Author(s) -
Н. Н. Тимошкина,
Olga A. Bogomolova,
И. А. Жужеленко,
Sergey N. Kabanov,
Elena A. Kalabanova,
Irina S Mitashok,
Ya. V. Svetitskaya,
Д. И. Водолажский
Publication year - 2019
Publication title -
sibirskij onkologičeskij žurnal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.115
H-Index - 4
eISSN - 2312-3168
pISSN - 1814-4861
DOI - 10.21294/1814-4861-2018-17-6-49-56
Subject(s) - dpyd , irinotecan , genotyping , colorectal cancer , genotype , fluorouracil , medicine , pharmacogenomics , pharmacogenetics , allele , chemotherapy , oncology , allele frequency , gastroenterology , pharmacology , cancer , biology , genetics , gene
Background. The personalized approach implies an individual choice of medicines and their doses for the patient, providing the most effective and safe pharmacotherapy. Objective: analysis of the frequencies of UGT1A1 and DPYD polymorphisms and comparison of genotyping data with irinotecan and 5-fluorouracil-induced toxicity, respectively. Materials and Methods . Venous blood of 94 Caucasian patients (46 men and 48 women, median age 61 years). The *6 and *28 UGT1A1 alleles were identified by pyrosequencing, and the *2А DPYD allele was identified by Real-time PCR. Results. The genotyping of 94 patients with colon cancer did not reveal the *2A SNP in the DPYD gene. The frequency rate of the *6 and *28 alleles of the UGT1A1 gene was 0.346 and 0.016, respectively. 24 % of patients receiving chemotherapy with 5-fluorouracil developed side effects associated with the circulatory system and the gastrointestinal tract. Hematological and nonhematological toxic reactions were noted in 48 % and 50 % of patients receiving irinotecan. Severe bilirubinemia was associated with the *28/*28 UGT1A1 genotype. The presence of a high-risk genotype (*28/*1, *28/*28 UGT1A1) correlated with the development of side effects (p=0.040). Conclusion. The absence of carriers of the *2А DPYD allele in the sample with a significant proportion of pronounced adverse toxic reactions to 5-fluorouracil causes the need for the inclusion of new polymorphisms of the DPYD gene in pharmacogenetic testing. The inclusion of genotyping of UGT1A1 polymorphisms into a complex of preliminary examination is advisable when planning treatment with irinotecan.