Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer

Breast Cancer. 2016 Mar;23(2):195-201. doi: 10.1007/s12282-014-0547-x. Epub 2014 Jul 10.

Abstract

Background: Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear.

Methods: This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer.

Results: The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P = 0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not.

Conclusion: Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

Keywords: Breast cancer; Cyclophosphamide; Epirubicin; GSTP1; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cyclophosphamide / administration & dosage
  • Epirubicin / administration & dosage
  • Febrile Neutropenia / chemically induced
  • Febrile Neutropenia / diagnosis
  • Febrile Neutropenia / genetics*
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Staging
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Epirubicin
  • Cyclophosphamide
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Fluorouracil