Relationship between ABCB1 gene polymorphisms and severe neutropenia in patients with breast cancer treated with doxorubicin/cyclophosphamide chemotherapy
| Autor: | Masahiro Hatori, Yutaro Iwabe, Midori Ikeda, Ryo Makuta, Daiki Tsuji, Yong-Il Kim, Mitsuru Shiokawa, Keisuke Yamamoto, Hidenori Nakamichi, Kunihiko Itoh, Kazuyuki Inoue, Hideki Hayashi, Takashi Daimon |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
medicine.medical_specialty Heterozygote ATP Binding Cassette Transporter Subfamily B Neutropenia Cyclophosphamide medicine.medical_treatment Pharmaceutical Science Breast Neoplasms Gastroenterology Polymorphism Single Nucleotide Severity of Illness Index Breast cancer Gene Frequency Risk Factors Internal medicine Genotype Antineoplastic Combined Chemotherapy Protocols Odds Ratio Medicine Humans Pharmacology (medical) Doxorubicin Genetic Predisposition to Disease Adverse effect Retrospective Studies Pharmacology Chemotherapy Chi-Square Distribution business.industry Homozygote Odds ratio Middle Aged medicine.disease Logistic Models Phenotype Immunology Multivariate Analysis Female business medicine.drug |
| Zdroj: | Drug metabolism and pharmacokinetics. 30(2) |
| ISSN: | 1880-0920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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