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Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy - PubMed

  • ️Thu Jan 01 2015

Review

. 2015 Mar 15;559(1):31-7.

doi: 10.1016/j.gene.2015.01.010. Epub 2015 Jan 10.

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Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy

Xiangxiang Ding et al. Gene. 2015.

Abstract

Background: The aim of this study was to ascertain whether single nucleotide polymorphisms of cytidine deaminase (CDA), a key enzyme in the metabolism pathway of gemcitabine, could predict clinical outcomes of cancer patients with gemcitabine-based chemotherapy.

Methods: We searched MEDLINE and EMBASE up to January 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according to the Newcastle-Ottawa Quality Assessment Scale. For each included study, the overall survival (OS), overall response rate (ORR) and toxicities were extracted and pooled using random-effects model.

Results: In total, data from 13 studies were included. CDA 208A>G and CDA 435C>T were not included in quantified synthesis due to limited data. CDA 79A>C polymorphism was not significantly associated with OS; however, patients carrying the variant CDA 79C allele were likely to have a poor survival, hazard ratio (HR)=1.03, 95% CI 0.957-1.27 (AC+CC vs. AA). CDA 79A>C polymorphism did not correlated with ORR, odds ratio (OR)=0.719, 95% CI 0.363-1.425 (AC+CC vs. AA). However, patients with the variant CDA 79C allele would experience more grade ≥ 3 leucopenia (OR=2.933, 95% CI 1.357-6.605) and tended to have more severe neutropenia (OR=1.313, 95% CI 0.157-10.981).

Conclusions: These results suggest that CDA 79A>C polymorphisms is a potential biomarker for toxicity of gemcitabine-based chemotherapy and a CDA testing before gemcitabine administration is preferred.

Keywords: Chemotherapy; Cytidine deaminase; Gemcitabine; Single nucleotide polymorphism.

Copyright © 2015 Elsevier B.V. All rights reserved.

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