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UGT1A1 polymorphisms in cancer: impact on irinotecan treatment

Authors Takano M, Sugiyama T

Received 21 November 2016

Accepted for publication 19 January 2017

Published 28 February 2017 Volume 2017:10 Pages 61—68

DOI https://doi.org/10.2147/PGPM.S108656

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


Masashi Takano1 Toru Sugiyama2

1Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Saitama, 2Department of Obstetrics and Gynecology, Iwate Medical University, Morioka, Iwate, Japan

Abstract: Mutations in the UGT1A1 gene have been implicated in Gilbert syndrome, which shows mild hyperbilirubinemia, and a more aggressive childhood subtype, Crigler–Najjar syndrome. To date, more than 100 variants have been found in the UGT1A1 gene. Among them, UGT1A1*28 and UGT1A1*6 have been reported to be associated with severe toxicities in patients treated with irinotecan-based chemotherapy by increasing the dose of SN-38 (7-ethyl-10-hydroxycamptothecin), an active form of irinotecan. Many association studies and meta-analyses have demonstrated the contribution of UGT1A1*28 and UGT1A1*6 polymorphisms to the toxicities caused by irinotecan-based therapy. The aim of this review was to evaluate the impact of these variants upon the toxicities and the efficacy of irinotecan-based chemotherapy.

Keywords: UGT1A1, irinotecan, chemotherapy, toxicity, response, survival
 

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