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

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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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Acknowledgments

This work was supported by the Grant 81172094 and 81101816 from the National Science Foundation of China, Grant 2011-WS-005 from the Six Talents Peak Foundation of Jiangsu Province, Grants BK2011095, BY2012185, BK2011271 and BK2011044 from the Natural Science Foundation of Jiangsu Province, China, Grant 2014CB744501 of the National Basic Research Program of China (973 Program) and the Grant KF-GN-201204 from State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University to GXX. Thanks very much to Tian-Tian Wang for her help of revise.

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Authors and Affiliations

  1. Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China

    Lei Cheng, Jing Hu, Wei Ren, Li Xie, Bao-Rui Liu & Xiao-Ping Qian

  2. Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

    Ming Li, Gen-Xing Xu & Xiao-Liang Dong

  3. School of Life Sciences, Zhejiang University, Hangzhou, 310058, China

    Zhan-Peng Sun

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  1. Lei Cheng
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Lei Cheng and Ming Li have contributed equally to this work.

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Cheng, L., Li, M., Hu, J. et al. UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians. Cancer Chemother Pharmacol 73, 551–560 (2014). https://doi.org/10.1007/s00280-014-2382-3

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