Associations between UGT1A1*6 or UGT1A1*6/*28 polymorphisms and irinotecan-induced neutropenia in Asian cancer patients
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- 作者：Fei-fei Han (1)
Chang-long Guo (2) (3)
Dan Yu (4)
Jin Zhu (1)
Li-li Gong (1)
Guang-run Li (1)
Ya-li Lv (1)
He Liu (1)
Guang-yu An (4)
Li-hong Liu (1) - 关键词：UGT1A1*6 ; UGT1A1*6/*28 ; Neutropenia ; Irinotecan ; Asian cancer population
- 刊名：Cancer Chemotherapy and Pharmacology
- 出版年：2014
- 出版时间：April 2014
- 年：2014
- 卷：73
- 期：4
- 页码：779-788
- 全文大小：962 KB
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Chang-long Guo (2) (3)
Dan Yu (4)
Jin Zhu (1)
Li-li Gong (1)
Guang-run Li (1)
Ya-li Lv (1)
He Liu (1)
Guang-yu An (4)
Li-hong Liu (1)
1. Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China
2. Reproductive and Genetic Center of National Research Institute for Family Planning, 100081, Beijing, China
3. Graduate School of Peking Union Medical College, 100730, Beijing, China
4. Oncology Department of Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China - ISSN：1432-0843
文摘
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-.688; P?=?0.000 (*6/*6 vs. *1/*6 or *1/*1)], [OR 1.542; 95?% CI 1.180-.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-.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.