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

Cancer Chemother Pharmacol. 2014 Apr;73(4):779-88. doi: 10.1007/s00280-014-2405-0. Epub 2014 Feb 12.

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.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Asian People / genetics*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Glucuronosyltransferase / genetics*
  • Humans
  • Irinotecan
  • Molecular Sequence Data
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neutropenia / chemically induced*
  • Neutropenia / enzymology
  • Neutropenia / genetics*
  • Polymorphism, Single Nucleotide
  • Topoisomerase I Inhibitors / adverse effects

Substances

  • Topoisomerase I Inhibitors
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Camptothecin