Correlation of UGT1A1^*28 and ^*6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients

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• 作者：Chalirmporn Atasilp^a ; ^b ; Pichai Chansriwong^c ; Ekapob Sirachainan^c ; Thanyanan Reungwetwattana^c ; Montri Chamnanphon^a ; ^b ; Apichaya Puangpetch^a ; ^b ; Sansanee Wongwaisayawan^d ; Chonlaphat Sukasem^a ; ^b ; ^{chonlaphat.suk@mahidol.ac.th" class="auth_mail" title="E-mail the corresponding author}
• 关键词：UGT1A1*28 ; UGT1A1*6 ; Neutropenia ; Irinotecan ; Colorectal cancer
• 刊名：Drug Metabolism and Pharmacokinetics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：31
• 期：1
• 页码：90-94
• 全文大小：210 K

文摘

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.