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Associations between UGT1A1*6 or UGT1A1*6/*28 polymorphisms and irinotecan-induced neutropenia in Asian cancer patients

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Abstract

Purpose

Neutropenia is a life-threatening side effect of irinotecan, and uridine diphosphate glucuronosyltransferases (UGTs) gene polymorphisms are considered to be one of the predictive markers of irinotecan-related toxicities. Many studies have demonstrated that patients bearing UGT1A1*28 have a higher risk of severe neutropenia on toxicity of irinotecan. However, UGT1A1 (TA7/TA7) was very rare in Asian populations. Some researches reported that UGT1A1*28 and/or UGT1A1*6 could predict irinotecan-induced toxicities in Asian populations, but controversial conclusions still remained. This study aims to investigate the association between UGT1A1 gene polymorphisms *6, *6/*28 and irinotecan-related neutropenia in Asian cancer patients receiving irinotecan regimen chemotherapy.

Experimental design

Meta-analyses were done to assess the relationship between UGT1A1*6 or UGT1A1*6/*28 and irinotecan-induced neutropenia.

Results

The risk of neutropenia was significantly higher among patients with a UGT1A1*6 genotype than among those carrying the UGT1A1*1 allele(s) [odds ratio (OR) 3.276; 95 % confidence interval (CI) 1.887–5.688; P = 0.000 (*6/*6 vs. *1/*6 or *1/*1)], [OR 1.542; 95 % CI 1.180–2.041; P = 0.001 (*6/*6 or *1/*6 vs. *1/*1)]. Also, the risk was significantly higher among patients with a UGT1A1*6/*28 than among those carrying the UGT1A1*1 allele(s) [OR 3.275; 95 % CI 2.152–4.983; P = 0.000 (*6/*6 or *28/*28 or *6/*28 vs. *1/*6 or *1/*28 or *1/*1)].

Conclusions

In conclusion, the UGT1A1*6 and UGT1A1*6/*28 genotypes were associated with an increased risk of irinotecan-induced neutropenia in Asian cancer patients.

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Acknowledgments

This research was financially supported by 81172986 National Natural Science Foundation.

Conflict of interest

All authors declare no conflicts of interest.

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Authors and Affiliations

  1. Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China

    Fei-fei Han, Jin Zhu, Li-li Gong, Guang-run Li, Ya-li Lv, He Liu & Li-hong Liu

  2. Reproductive and Genetic Center of National Research Institute for Family Planning, 100081, Beijing, China

    Chang-long Guo

  3. Graduate School of Peking Union Medical College, 100730, Beijing, China

    Chang-long Guo

  4. Oncology Department of Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China

    Dan Yu & Guang-yu An

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  1. Fei-fei Han
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  2. Chang-long Guo
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Correspondence to Fei-fei Han.

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Fei-fei Han and Chang-long Guo have contributed equally to this work.

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280_2014_2405_MOESM1_ESM.tif

The Egger’s funnel plot for the publication bias test. A) *6/*6 versus *1/*6 or *1/*1, B) *6/*6 or *1/*6 versus *1/*1, C) *6/*6 or *28/*28 or *6/*28 versus *1/*6 or *1/*28 or *1/*1 (TIFF 1063 kb)

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Han, Ff., Guo, Cl., Yu, D. et al. Associations between UGT1A1*6 or UGT1A1*6/*28 polymorphisms and irinotecan-induced neutropenia in Asian cancer patients. Cancer Chemother Pharmacol 73, 779–788 (2014). https://doi.org/10.1007/s00280-014-2405-0

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