Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer
Loading...
Date
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Verlag
Abstract
Purpose: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6∗4 (rs2279343), CYP2B6∗5 (rs3211371) and CYP2B6∗9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. Methods: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. Results: The minor allele frequencies of CYP2B6∗9, CYP2B6∗4 and CYP2B6∗5 were 0.27, 0.29 and 0.07, respectively. CYP2B6∗5/∗6,∗6/∗9 or∗6/∗6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. Conclusions: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms. © 2014 Springer-Verlag Berlin Heidelberg.
Description
Keywords
Breast cancer, Cyp2b6∗cyclophosphamide, Pharmacogenetics, Adult, Alleles, Antineoplastic agents, alkylating, Antineoplastic combined chemotherapy protocols, Breast, Breast neoplasms, Cohort studies, Cyclophosphamide, Cytochrome p-450 cyp2b6, Female, Gene frequency, Genetic association studies, Humans, Lebanon, Middle aged, Myelopoiesis, Neoplasm grading, Neoplasm recurrence, local, Neoplasm staging, Polymorphism, genetic, Polymorphism, single nucleotide, Retrospective studies, Survival analysis, Cytochrome p450 2b6, Docetaxel, Doxorubicin, Epirubicin, Erythropoietin, Fluorouracil, Granulocyte colony stimulating factor, Hemoglobin, Iron, Methotrexate, Trastuzumab, Alkylating agent, Antineoplastic agent, Cyp2b6 protein, human, Article, Blood toxicity, Breast carcinoma, Cancer combination chemotherapy, Cancer patient, Cancer recurrence, Cancer survival, Drug dose reduction, Drug efficacy, Drug safety, Erythrocyte concentrate, Erythrocyte transfusion, Febrile neutropenia, Gene linkage disequilibrium, Genotype, Haplotype, Homozygote, Human, Lebanese, Leukocyte count, Major clinical study, Medical record review, Multiple cycle treatment, Neutrophil count, Peripheral neuropathy, Priority journal, Single nucleotide polymorphism, Allele, Cancer grading, Cancer staging, Cohort analysis, Drug effects, Genetic association, Genetic polymorphism, Genetics, Metabolism, Pathology, Retrospective study, Survival