Background. Many studies have reported an association between genetic variants of the UGT1A gene (uridine diphosphate-glucuronosyltransferase, UGT) and the development of toxicities. Considerable ethnic differences in genetic variations of the UGT1A locus have also been observed. The aim of this study was to comprehensively investigate genetic variation in UGT1A1/UGT1A7/UGT1A9, in order to evaluate the clinical influences of toxicities and subsequent outcome in Taiwanese patients undergoing irinotecan-based chemotherapy.Patients and Methods. One hundred and fifteen patients with metastatic colorectal cancer treated with irinotecan based chemotherapy were recruited. Genomic DNA was extracted from peripheral blood and genotyped using PCR-based methods. We analyzed the association between UGT1A genotypes and development of toxicities and response to chemotherapy. Results. Only one of the 115 patients (0.9%) was homozygous for UGT1A1*28 in this study. We observed a significant correlation between the low activity UGT1A1*28 genotypes and increasing incidence of neutropenia (odds ratio 2.42, p=0.049). There was also a trend of association between UGT1A1*6 [211G>A] genotype and the incidence of neutropenia (odds ratio 2.18, p=0.084) and between association between UGT1A7 [622T>C] genotype and the incidence of neutropenia (odds ratio 2.05, p=0.087). By genotype, patients with homozygous UGT1A7 [387G/G] showed a significantly lower response rate (31.2% vs. 61.8%, OR=0.28, p=0.049). Patients with UGT1A haplotype II also showed marginally significantly lower response rates (31.3% vs. 66.7%, OR=0.23, p=0.053). Conclusion. Genotyping of UGT1As polymorphisms provides significant predictors for neutropenia occurrence and tumour responses in metastatic CRC patients receiving a FOLFIRI regimen.
Background. Many studies have reported an association between genetic variants of the UGT1A gene (uridine diphosphate-glucuronosyltransferase, UGT) and the development of toxicities. Considerable ethnic differences in genetic variations of the UGT1A locus have also been observed. The aim of this study was to comprehensively investigate genetic variation in UGT1A1/UGT1A7/UGT1A9, in order to evaluate the clinical influences of toxicities and subsequent outcome in Taiwanese patients undergoing irinotecan-based chemotherapy.Patients and Methods. One hundred and fifteen patients with metastatic colorectal cancer treated with irinotecan based chemotherapy were recruited. Genomic DNA was extracted from peripheral blood and genotyped using PCR-based methods. We analyzed the association between UGT1A genotypes and development of toxicities and response to chemotherapy. Results. Only one of the 115 patients (0.9%) was homozygous for UGT1A1*28 in this study. We observed a significant correlation between the low activity UGT1A1*28 genotypes and increasing incidence of neutropenia (odds ratio 2.42, p=0.049). There was also a trend of association between UGT1A1*6 [211G>A] genotype and the incidence of neutropenia (odds ratio 2.18, p=0.084) and between association between UGT1A7 [622T>C] genotype and the incidence of neutropenia (odds ratio 2.05, p=0.087). By genotype, patients with homozygous UGT1A7 [387G/G] showed a significantly lower response rate (31.2% vs. 61.8%, OR=0.28, p=0.049). Patients with UGT1A haplotype II also showed marginally significantly lower response rates (31.3% vs. 66.7%, OR=0.23, p=0.053). Conclusion. Genotyping of UGT1As polymorphisms provides significant predictors for neutropenia occurrence and tumour responses in metastatic CRC patients receiving a FOLFIRI regimen.