Abstract
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.
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