title: Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based chemotherapy.
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.
authors.affiliation: First Clinical College, Nanjing Medical University, Nanjing 210029, China; Department of Radiology, Nanjing Drum Tower Hospital, Nanjing 210008, China.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Ding
authors.affiliation: First Clinical College, Nanjing Medical University, Nanjing 210029, China; Department of Oncology, Nanjing Drum Tower Hospital, Nanjing 210008, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Radiology, Nanjing Drum Tower Hospital, Nanjing 210008, China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Radiology, Nanjing Drum Tower Hospital, Nanjing 210008, China. Electronic address: glyyyxk@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000483:Alleles; D000964:Antimetabolites, Antineoplastic; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000201:enzymology / Q000401:mortality; D003564:Cytidine Deaminase / Q000235:genetics*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016239:MEDLINE; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D011110:Polymorphism, Genetic; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D005819:Genetic Markers; D009363:Neoplasm Proteins; D003841:Deoxycytidine; D003564:Cytidine Deaminase; D000093542:Gemcitabine
keywords: Chemotherapy; Cytidine deaminase; Gemcitabine; Single nucleotide polymorphism