Relationship between UDP-glucuronosyltransferase 1A1 gene polymorphisms and toxicity in patients with cancer treated with irinotecan-based chemotherapy

Abstract

Objective To investigate the incidence and severity of adverse events in pateints with solid tumor treated with irinotecan-based chemotherapy,and their relationship with UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms.Methods Sixty-seven tumor patients treated with irinotecan-based chemotherapy were enrolled.Genomic DNA was extracted from peripheral blood,and the UGT1 A1 * 28 and UGT1 A1 * 6 genotypes were determined by direct sequencing.The adverse events during therapy were observed.The relationship between UGT1A 1 gene polymorphisms and toxicity of irinotecan was analyzed.Results The distribution of the genotypes in 67 cancer patients was as follows:UGT1 A1 * 28 wild type genotype TA6/6 (51,76.1％),heterozygous genotype TA6/7 (12,17.8％),and homozygous genotype TA7/7 (4,6.0％); UGT1A1 * 6 wild type genotype G/G (43,64.2％),heterozygous genotype G/A (18,26.9％),and homozygous genotype A/A (6,9.0％).The incidence of grade 3 and 4 diarrhea and thrombocytopenia in the patients with UGT1A1 * 28 (TA6/7 and TA7/7) was 56.3％ and 31.3％ respectively,significantly higher than 25.5％ and 13.7％ in the patient with wild type UGT1A1 * 28 (TA6/6).The incidence of grade 3-4 diarrhea in the patients with UGT1A1 * 6 (G/A + A/A) was 50.0％,significantly higher than 1 1.6％ in the patient with wild type UGT1 A1 * 6 (G/G).Toxicity rate in patients with the non-wild type UGT1 A1 gene polymorphisms was significantly higher than that in the patients with wild type UGT1A1 gene (P＜0.05).Conclusion The UGT1A1 * 28 (TA6/7 and TA7/7) genotypes increase the risk of grade 3-4 diarrhea or thrombocytopenia,and the UGT1A1 * 6 (G/A and A/A) genotypes increase the risk of grade 3-4 diarrhea in tumor patients treated with irinotecan-based chemotherapy. Key words: UDP-glucuronosyltransferase 1A1 ; Gene polymorphisms; Irinotecan