Relationship between ABCB1 gene polymorphisms and severe neutropenia in breast cancer patients treated with doxorubicin/cyclophosphamide chemotherapy
演題番号 : P103-2
1:Department of Clinical Pharmacology and Genetics School of Pharmaceutical Sciences University of Shizuoka、2:Seirei Hamamatsu General Hospital、3:Seirei Hamamatsu General Hospital
Chemotherapy-induced neutropenia is one of the major adverse events which results in reduction of chemotherapy. Doxorubicin is known to be a substrate of ABCB1 transporter and it has been reported that ABCB1 gene polymorphisms influence pharmacokinetics of doxorubicin. The aim of this study was to evaluate the association between severe neutropenia and ABCB1 gene polymorphisms in breast cancer patients.
Breast cancer patients treated with doxorubicin/cyclophosphamide chemotherapy were investigated. Peripheral blood samples from patients were used to genotype ABCB1 2677G>T,A and 3435C>T polymorphisms. Genotypes were investigated for their association with grade 3 or greater neutropenia. Potential risk factors associated with grade 3 or greater neutropenia were evaluated using univariate and multivariate logistic regression models and reported as odds ratio (OR) with 95% confidence intervals (CIs).
One hundred and forty-one female patients were analyzed. The median of age was 54 years and the median dose of doxorubicin and cyclophosphamide for each cycle was 60 mg/m2 and 600 mg/m2, respectively.
We observed a significant association between the ABCB1 2677G>T,A polymorphism and the proportion of patients with grade 3 or greater neutropenia. The proportion of grade 3 or greater neutropenia were 85.7% in the homozygous variant group and 80.0% and 58.6% in the heterozygous variant and GG genotype group, respectively (p=0.021). In multivariate logistic regression revealed that ABCB1 2677G>T,A was found to be a strong predictor of grade 3 or greater neutropenia (OR: 3.25; 95%CI: 1.343-7.853, p=0.009).
The present results suggest that ABCB1 2677G>T,A is one of the predictive factors associated with severe neutropenia. It has been reported that 2677G>T,A was associated with lower levels of P-glycoprotein, so it is possible that variant allele causes the decrease of doxorubicin efflux and results in the increase of severe neutropenia.