ABCB1 polymorphism as a predictive biomarker for amrubicin-induced neutropenia

Anticancer Res. 2014 Jul;34(7):3517-22.

Abstract

Background: Amrubicin is a promising therapy for lung cancer, but is associated with a high incidence of severe neutropenia. The present study assessed the utility of ABCB1 and NAD(P)H quinone oxidoreductase 1 (NQO1) polymorphism as a predictor of amrubicin-induced neutropenia.

Materials and methods: Fifty-four Japanese lung cancer patients who received amrubicin chemotherapy were consecutively recruited and toxicities and SNPs (MDR1; C1236T, C3435T and G2677T/A, NQO1; C609T) were evaluated.

Results: The incidence of neutropenia was higher in patients treated with 40 mg/m2 of amrubicin (n=32) compared to patients treated with 35 mg/m2 of amrubicin (n=22) (53.1% vs. 22.7%). Patients who were homogenous for the wild-type allele of C3435T were at significantly higher risk of neutropenia compared to patients with other genotypes. By contrast, the C609T genotype of NQO1 was not related to neutropenia.

Conclusion: C3435T polymorphisms of ABCB1 might be able to predict severe amrubicin-induced neutropenia.

Keywords: ABCB1; Amrubicin; lung cancer; neutropenia; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Aged
  • Aged, 80 and over
  • Alleles
  • Anthracyclines / administration & dosage
  • Anthracyclines / adverse effects*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • Neutropenia / chemically induced*
  • Polymorphism, Single Nucleotide

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anthracyclines
  • Antineoplastic Agents
  • amrubicin
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human