title: Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients: A hospital-based observational study.
abstract: Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22-9.69; P = 0.020), CYP2B6*6 (OR, 4.51; 95% CI, 1.21-16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15-41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06-8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia.
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka Department of Pharmacy Department of Medical Oncology, Seirei Hamamatsu General Hospital, Hamamatsu Department of Drug Evaluation and Informatics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.forename: Midori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Harumi
authors.initials: H
authors.lastname: Nakamori
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Aki
authors.initials: A
authors.lastname: Otake
authors.forename: Mari
authors.initials: M
authors.lastname: Yokoi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Keita
authors.initials: K
authors.lastname: Hirai
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakamichi
authors.forename: Umi
authors.initials: U
authors.lastname: Tokou
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shiokawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006760:Hospitalization; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index