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Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
UGT1A1 polymorphisms in cancer: impact on irinotecan treatment
Masashi Takano1, Toru Sugiyama2
1Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Saitama.
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.
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