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01-03-2014 | Original Article

UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians

Authors: Lei Cheng, Ming Li, Jing Hu, Wei Ren, Li Xie, Zhan-Peng Sun, Bao-Rui Liu, Gen-Xing Xu, Xiao-Liang Dong, Xiao-Ping Qian

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2014

Abstract

Purpose

Previous studies confirmed that genotyping uridine diphosphate glucuronosyltransferase (UGT) 1A1*28 polymorphisms could predict the side effects in cancer patients using irinotecan (IRI) and then reduce IRI-induced toxicity by preventative treatment or decrease in dose. However, the association between UGT1A1*6 polymorphisms and IRI-induced severe toxicity in Asian patients is still unclear. The aim of this study was to evaluate the association between UGT1A1*6 polymorphisms and IRI-induced severe neutropenia as well as diarrhea in Asian patients.

Methods

We searched all papers on PubMed and Embase from February 1998 to August 2013. Then we assessed the methodologies quality, extracted data and made statistics analysis using STATA software. To uncover the sources of heterogeneity, subgroup meta-analysis was conducted according to the dosage of IRI.

Results

Eleven papers were included according to the inclusion and exclusion criteria after searching Pubmed and Embase. Overall, an increased risk of severe toxicity in Asian patients with UGT1A1*6 polymorphisms was found. Patients with heterozygous variant of UGT1A1*6 showed an increased risk [odds ratio (OR) = 1.98, 95 % confidence intervals (CI) 1.45–2.71, P < 0.001], and homozygous mutation showed an even higher risk (OR = 4.44, 95 % CI 2.42–8.14, P < 0.001) for severe neutropenia. For severe diarrhea, heterozygous variant of UGT1A1*6 showed no significant risk, while the homozygous variant performed a notable risk (OR = 3.51, 95 % CI 1.41–8.73, P = 0.007). Subgroup meta-analysis indicated that for patients harboring either heterozygous or homozygous variant, low dose of IRI also presented comparably increased risk in suffering severe neutropenia.

Conclusion

In this meta-analysis, UGT1A1*6 polymorphisms were revealed as potential biomarkers, predicting IRI-induced severe toxicity in patients from Asia, and increased incidences of severe neutropenia could occur in both high/medium and low doses of IRI.

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Title: UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians
Authors: Lei Cheng
Ming Li
Jing Hu
Wei Ren
Li Xie
Zhan-Peng Sun
Bao-Rui Liu
Gen-Xing Xu
Xiao-Liang Dong
Xiao-Ping Qian
Publication date: 01-03-2014
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2382-3

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