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The influence of cytidine deaminase ‐33delC polymorphism on treatment outcome with high‐dose cytarabine in Chinese patients with relapsed acute myeloid leukaemia
Author(s) -
He H.,
Liu Z. Q.,
Li X.,
Yin J. Y.,
Zhai M.,
Zhou H. H.
Publication year - 2015
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12309
Subject(s) - medicine , cytarabine , gastroenterology , odds ratio , oncology , cytidine deaminase , chemotherapy , immunology , antibody
Summary What is known and 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 ( SNP s) ‐ 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. Results and discussion 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). What is new and conclusion 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.