title: The influence of cytidine deaminase -33delC polymorphism on treatment outcome with high-dose cytarabine in Chinese patients with relapsed acute myeloid leukaemia.
abstract: OBJECTIVE
  Identification of biomarkers that could predict high-dose cytarabine (Ara-C) efficacy and toxicity is a key issue in individualized therapy. The aim of our study was to evaluate the influence of cytidine deaminase (CDA) single nucleotide polymorphisms (SNPs) -451G>A (rs532545), 435C>T (rs1048977) and -33delC (rs3215400) on treatment outcome in patients with relapsed acute myeloid leukaemia (AML) after high-dose Ara-C chemotherapy.
  
  
  METHODS
  In total, 173 patients with relapsed AML, treated with high-dose Ara-C chemotherapy, were genotyped for three polymorphisms in CDA gene using the allele-specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays. Binary logistic regression was used to evaluate the influence of selected polymorphisms on tumour response and occurrence of treatment-related toxicity.
  
  
  CONCLUSIONS
  The CC genotype at -33delC, a promoter polymorphism, increased the odds of overall response rate (odds ratio [OR] = 5·125; 95% confidence intervals (CI) = 2·446-10·74; P = 0·0008) and grade ≥3 infection toxicity incidence rate (OR = 3·572; 95% CI = 1·68-7·594; P = 0·003). In multivariable analysis, this polymorphism was a potential independent prognostic marker for the risk of overall response (P = 0·011), but not grade ≥3 infection toxicity incidence rate (P = 0·49). Two other polymorphisms, -451G>A and 435C>T, did not influence treatment outcome, including overall response rate, infection toxicity and nausea/vomiting, in patients with relapsed AML (P > 0·05).
  
  
  CONCLUSIONS
  The findings suggest that CDA -33delC variant might be a potential marker for predicting treatment outcome in Chinese patients with relapsed AML given high-dose cytarabine chemotherapy.
authors.affiliation: Research laboratory, Liaoning province Benxi Central Hospital, Liaoning Benxi, China.|Department of Hematology, Liaoning Province Benxi Central Hospital, Liaoning Benxi, China.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: H
authors.initials: H
authors.lastname: He
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhai
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Zhou
keywords: cytarabine; cytidine deaminase; single nucleotide polymorphism; treatment outcome