Atasilp Chalirmporn, Chansriwong Pichai, Sirachainan Ekapob, Reungwetwattana Thanyanan, Chamnanphon Montri, Puangpetch Apichaya, Wongwaisayawan Sansanee, Sukasem Chonlaphat
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Laboratory for Pharmacogenomics, Clinical Pathology, Somdetch Phra Debharatana Medical Centre, Ramathibodi Hospital, Bangkok, Thailand.
Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Drug Metab Pharmacokinet. 2016 Feb;31(1):90-94. doi: 10.1016/j.dmpk.2015.12.004. Epub 2015 Dec 31.
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.
尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）基因多态性与伊立替康毒性有关。本研究旨在确定泰国转移性结直肠癌患者中UGT1A1（）28和（）6基因多态性与伊立替康毒性之间的关联。44例转移性结直肠癌患者接受了以伊立替康为基础的化疗。在治疗的第1周期和第2周期测定血液学毒性。采用焦磷酸测序技术分析UGT1A1（）28和（）6的基因型。UGT1A1（）28和（）6基因多态性的基因检测频率分别为22.8%（TA6/TA7；20.5%，TA7/TA7；2.3%）和15.9%（GA）。没有患者为纯合子UGT1A1（）6（AA）。UGT1A1（）28和（）6基因多态性均与严重血液学毒性无显著关联。然而，联合分析UGT1A1（）28和（）6发现，其与第1周期和第2周期的严重中性粒细胞减少有关（P分别为0.044和0.017）。UGT1A1（）28和（*）6基因多态性可能增加泰国结直肠癌患者发生伊立替康诱导的中性粒细胞减少的风险。
Zotero 插件