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Sukasem C.,Mahidol University | Sukasem C.,Somdetch Phra Debharatana Medical Center | Atasilp C.,Mahidol University | Atasilp C.,Somdetch Phra Debharatana Medical Center | And 6 more authors.
Journal of Clinical Laboratory Analysis

Background: UGT1A1 is a polymorphic enzyme that has been associated with irinotecan drug metabolisms. We developed a pyrosequencing method to detect allele frequency and genotype of UGT1A1 polymorphisms (UGT1A1*28 and UGT1A1*6) in Thai colorectal cancer patients. Method: A pyrosequencing method was designed to determine UGT1A1 genetic polymorphisms including UGT1A1*28 (A[TA]7TAA) and UGT1A1*6 (211G>A) in 91 Thai colorectal cancers. Result: Genotyping by the pyrosequencing technique was 100% concordant with capillary electrophoresis sequencing. The allele frequencies for UGT1A1 genetic polymorphisms were *1/*1 (54.95%), *1/*6 (13.19%), *1/*28 (25.27%), *28/*6 (4.40%), and *28/*28 (2.20%). No homozygous mutation UGT1A1*6 was found in our population. Conclusions: We developed a rapid, reliable, more cost-effective, and simple assay to detect UGT1A1 genetic polymorphisms in routine practice before initiating irinotecan therapy. The UGT1A1*28 and UGT1A1*6 alleles were found to be similar in the Asian populations. © 2016 Wiley Periodicals, Inc. Source

Atasilp C.,Mahidol University | Atasilp C.,Somdetch Phra Debharatana Medical Center | Chansriwong P.,Mahidol University | Sirachainan E.,Mahidol University | And 8 more authors.
Drug Metabolism and Pharmacokinetics

UDP-glucuronosyltransferase1A1 (UGT1A1) polymorphisms have been related with irinotecan toxicity. The purpose of this study was to determine the associations between UGT1A1∗28 and ∗6 polymorphisms and irinotecan toxicity in Thai patients with metastatic colorectal cancer. 44 metastatic colorectal cancer patients received irinotecan-based chemotherapy. Hematologic toxicities were determined in the first and second cycles of treatment. The genotypes of UGT1A1∗28 and ∗6 were analyzed by pyrosequencing technique. The frequencies of genetic testing for UGT1A1∗28 and ∗6 polymorphisms were 22.8% (TA6/TA7; 20.5%, TA7/TA7; 2.3%) and 15.9% (GA), respectively. No patients had the homozygous UGT1A1∗6 (AA). Neither UGT1A1∗28 nor UGT1A1∗6 polymorphisms were significantly associated with severe hematologic toxicities. However, analysis of UGT1A1∗28 and ∗6 in combination revealed an association with severe neutropenia in the first and second cycles (P = 0.044, P = 0.017, respectively). Both UGT1A1∗28 and ∗6 polymorphisms may have an increased risk of irinotecan-induced neutropenia in Thai colorectal cancer patients. © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved. Source

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