title: High incidence of severe neutropenia after gemcitabine-based chemotherapy in Chinese cancer patients with CDA 79A>C mutation.
abstract: Cytidine deaminase (CDA) is a crucial enzyme in gemcitabine inactivation. Mutations in CDA gene have been found to influence the activity of CDA enzyme, which might lead to altered pharmacokinetics profile and clinical outcome of gemcitabine. In this study, the screening for the presence of CDA 79A>C and CDA 208G>A was performed by allele-specific PCR and restriction fragment length polymorphism, respectively. No difference in CDA allele frequencies was found between Chinese cancer patients and healthy volunteers. The frequencies for CDA 79A>C and 208G>A in the studied population were 12.2% and 1.0%, respectively. While a high incidence of grade 3-4 neutropenia was noted as 5 out of 8 (62.5%) patients heterozygous or homozygous for CDA 79A>C mutation developed it, in patients homozygous for the wild-type allele, the incidence was only 17.2% (5 out of 29) (p=0.021). Our study suggests that CDA 79A>C mutation might be a potential risk factor of gemcitabine-induced neutropenia toxicity.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Xu
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Chen
authors.forename: Rongyuan
authors.initials: R
authors.lastname: Zhuang
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
authors.forename: Weimin
authors.initials: W
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D003564:Cytidine Deaminase / Q000235:genetics*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology*; D011110:Polymorphism, Genetic; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D003564:Cytidine Deaminase; D000093542:Gemcitabine