Relationship between ABCB1gene polymorphisms and severe neutropenia in patients with breast cancer treated with doxorubicin/cyclophosphamide chemotherapy

Autor: Ikeda, Midori, Tsuji, Daiki, Yamamoto, Keisuke, Kim, Yong-Il, Daimon, Takashi, Iwabe, Yutaro, Hatori, Masahiro, Makuta, Ryo, Hayashi, Hideki, Inoue, Kazuyuki, Nakamichi, Hidenori, Shiokawa, Mitsuru, Itoh, Kunihiko
Zdroj: Drug Metabolism and Pharmacokinetics; April 2015, Vol. 30 Issue: 2 p149-153, 5p
Abstrakt: 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, ABCB1polymorphisms influence doxorubicin pharmacokinetics. We evaluated the association between chemotherapy-induced neutropenia and ABCB1polymorphisms 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 ABCB12677G>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 ABCB12677G>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). ABCB1polymorphisms may influence the extent of chemotherapy-induced neutropenia in AC combination-treated patients with breast cancer.
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