title: An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel.
abstract: OBJECTIVE
  Docetaxel is one of the most widely used chemotherapy drugs for gynecological cancers. A dose-limiting factor of docetaxel is severe neutropenia, and previous reports showed that grade 4 neutropenia was observed in approximately 70% of Japanese patients treated with docetaxel. In order to elucidate a valid biomarker for docetaxel-induced neutropenia, we analyzed 42 Japanese patients with gynecological cancers such as ovarian cancer and endometrial cancer of the uterus.
  
  
  METHODS
  As a first step, AUC of docetaxel was examined in 10 patients and 1,936 SNPs of 225 genes were genotyped using DMET Plus™ genotyping systems.
  
  
  RESULTS
  The first screening revealed that 28 SNPs were associated with the AUC (P < 0.05), and we analyzed the associations between the 28 SNPs and neutrophil counts in the other 32 patients, with the result that CYP39A1 (rs7761731) was found to be the only SNP significantly associated (P = 0.049 OR = 9.0) with the incidence of grade 4 neutropenia among 28 SNPs.
  
  
  CONCLUSIONS
  This SNP in CYP39A1 may be a useful biomarker for predicting the risk of docetaxel-induced neutropenia.
authors.affiliation: Affiliated Field of Medical Genetics, Division of Biomedical Engineering and Science, Graduate Course of Medicine, Graduate School of Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kanno
authors.forename: Ken
authors.initials: K
authors.lastname: Ishitani
authors.forename: Hisaichi
authors.initials: H
authors.lastname: Fujii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohta
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019540:Area Under Curve; D000077143:Docetaxel; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D020641:Polymorphism, Single Nucleotide; D013250:Steroid Hydroxylases / Q000235:genetics*; D043823:Taxoids / Q000009:adverse effects* / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D013250:Steroid Hydroxylases; C499573:CYP39A1 protein, human