Polymorphic Variants of the UGT1A1, MTHFR, GSTP, and ITPA Genes and Response to Platinum-Based Chemotherapy in Patients with Bladder Cancer

— The aim of the study was to determine an association of the UGT1A1 (rs8175347), MTHFR (rs1801133), GSTP1 (rs1695), and ITPA (rs1127354) polymorphic variants with response to platinum-based chemotherapy in patients with bladder cancer. The study group consisted of 60 patients who were treated in the National Cancer Institute. The population control groups were formed from conditionally healthy adults from different regions of Ukraine. The commercial DNA extraction kits were used to isolate genomic DNA from the blood samples of patients and the control group. Genotyping of the MTHFR , GSTP1 , and ITPA alleles was carried out using PCR followed by RFLP analysis. The determination of UGT1A1 allelic variants was conducted by a method of fragment analysis of fluorescently labeled PCR products using an ALF-express II automatic laser analyzer. No significant difference was detected in the distribution of allele and genotype frequencies of the UGT1A1 , MTHFR , GSTP1 , and ITPA gene polymorphisms between the population sample and studied group of patients with bladder cancer. In addition, no statistically significant difference was detected in the distribution of allele and genotype frequencies for the polymorphic loci of the UGT1A1 , MTHFR , and ITPA genes in codominant, dominant, and recessive models between the groups of patients with bladder cancer who had a positive response to chemotherapy and those who had no response to the therapy. It was demonstrated that the frequency of the GSTP1 gene 313G allele (0.40) was statistically significantly higher in the group of patients who responded to chemotherapy than in the group of patients who did not respond to the treatment (0.22). It was established that carriers of the GSTP1 gene 313G allele (AG and GG genotypes) have a higher probability of a positive response to chemotherapy than individuals with the AA genotype (OR = 3.05; CI 95%: 1.053–8.838). It was demonstrated that the GSTP1 gene A313G polymorphism (rs1695) is associated with a response to chemotherapy with platinum-based drugs, including cisplatin. The presence of the 313G allele in the patient genotype can indicate a better sensitivity of the tumor to platinum-based drugs.