Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy

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 0.957-127 (AC + CC vs. AA). CDA 79A> C polymorphism did not correlated with ORR, odds ratio (OR) = 0.719,95% CI 0363-1.425 (AC + CC vs. AA). However, patients with the variant CDA 79C allele would experience more grade >= 3 leucopenia (OR = 2.933, 95% Cl 1357-6.605) and tended to have more severe neutropenia (OR = 1.313,95% Cl 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. (C) 2015 Elsevier B.V. All rights reserved.