title: Relationship between ABCB1 gene polymorphisms and severe neutropenia in patients with breast cancer treated with doxorubicin/cyclophosphamide chemotherapy.
abstract: Chemotherapy-induced neutropenia is one of the major adverse events which results in the reduction of chemotherapy. Doxorubicin is a substrate of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transporter; reportedly, ABCB1 polymorphisms influence doxorubicin pharmacokinetics. We evaluated the association between chemotherapy-induced neutropenia and ABCB1 polymorphisms in patients with breast cancer. We investigated 141 patients with breast cancer treated with doxorubicin and cyclophosphamide (AC) chemotherapy. Peripheral blood samples obtained from patients were genotyped for the ABCB1 2677G>T/A and 3435C>T polymorphisms. The genotypes were then investigated for their association with grade 3 or greater neutropenia, and further their risk factors were examined using a multivariate logistic regression. The proportion of patients with grade 3 or greater neutropenia was 85.7% in the homozygous variant group, and 80% and 58.6% in the heterozygous variant and GG genotype groups, respectively (p = 0.021). The multivariate logistic regression analysis revealed that the ABCB1 2677G>T/A polymorphism was a strong predictor of grade 3 or greater neutropenia (odds ratio: 3.76; 95% confidence interval: 1.44-9.81; p = 0.007). ABCB1 polymorphisms may influence the extent of chemotherapy-induced neutropenia in AC combination-treated patients with breast cancer.
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. Electronic address: d-tsuji@u-shizuoka-ken.ac.jp.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacy, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Medical Oncology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Iwabe
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatori
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Makuta
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Pharmacy, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakamichi
authors.affiliation: Department of Pharmacy, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shiokawa
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016009:Chi-Square Distribution; D003520:Cyclophosphamide / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D004317:Doxorubicin; D003520:Cyclophosphamide
keywords: Adenosine triphosphate-binding cassette subfamily B member 1 polymorphism; Breast neoplasms; Cyclophosphamide; Doxorubicin; Neutropenia