title: MDM2 SNP309 and TP53 R72P associated with severe and febrile neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide.
abstract: The aim of this study was to investigate the association of two genetic polymorphisms, MDM2 SNP309 and TP53 R72P, with incidence of neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide (FEC). Primary breast cancer patients (n = 216) treated with adjuvant FEC (60, 75 or 100 mg/m(2)) were included in this study. The association of genotypes of MDM2 SNP309 and TP53 R72P, determined by TaqMan SNP Genotyping Assays, with febrile neutropenia (FN) was investigated. In the patients treated with FEC100, G/G genotype for MDM2 SNP309 (G/G genotype( MDM2 )) was significantly (P < 0.01) associated with a lower incidence (5.3 vs. 39.2%) of severe neutropenia (<100/mm(3)) than with T/T + T/G genotypes( MDM2 ), and C/C genotype for TP53 R72P (C/C genotype( TP53 )) was significantly (P = 0.03) associated with a higher incidence (58.3 vs. 27.3%) of FN than with G/G + G/C genotypes( TP53 ). The combination of C/C genotype( TP53 ) and T/T + T/G genotype( MDM2 ) showed the highest risk for developing severe neutropenia (83.3%) and FN (62.5%) than any other combinations. In the patients treated with FEC60 or FEC75, there was no significant association of MDM2 SNP309 and TP53 R72P with severe neutropenia and FN. MDM2 SNP309 and TP53 R72P are significantly associated with severe neutropenia and FN, respectively, in breast cancer patients treated with FEC100, and especially their combination may be a useful predictor of severe neutropenia and FN.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Okishiro
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Ryo
authors.initials: R
authors.lastname: Tsunashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Kenzo
authors.initials: K
authors.lastname: Shimazu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.forename: Naomi
authors.initials: N
authors.lastname: Maruyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D056726:Genetic Association Studies; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D009503:Neutropenia / Q000139:chemically induced* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D003520:Cyclophosphamide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D005472:Fluorouracil