Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients.
Breast Cancer Res Treat
; 124(2): 593-8, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20632082
ABSTRACT
Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Paclitaxel
/
Neoplasias da Mama Masculina
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Polimorfismo de Nucleotídeo Único
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Sistema Enzimático do Citocromo P-450
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Taxoides
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Hipersensibilidade a Drogas
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Antineoplásicos Fitogênicos
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
País/Região como assunto:
Europa
Idioma:
En
Revista:
Breast Cancer Res Treat
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Itália