title: Associations between UGT1A1*6 or UGT1A1*6/*28 polymorphisms and irinotecan-induced neutropenia in Asian cancer patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Pharmacy Department of Beijing Chao-Yang Hospital, Capital Medical University, 100020, Beijing, China, hanfeifei@163.com.
authors: Fei-fei
authors: FF
authors: Han
authors: Chang-long
authors: CL
authors: Guo
authors: Dan
authors: D
authors: Yu
authors: Jin
authors: J
authors: Zhu
authors: Li-li
authors: LL
authors: Gong
authors: Guang-run
authors: GR
authors: Li
authors: Ya-li
authors: YL
authors: Lv
authors: He
authors: H
authors: Liu
authors: Guang-yu
authors: GY
authors: An
authors: Li-hong
authors: LH
authors: Liu
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D009503:Neutropenia / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D059004:Topoisomerase I Inhibitors / Q000009:adverse effects; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D059004:Topoisomerase I Inhibitors; D000099148:UGT1A1 Enzyme