Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer.
Pharmacogenomics J
; 7(5): 362-5, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-17224914
ABSTRACT
Paclitaxel is commonly used in the treatment of breast cancer. Variability in paclitaxel clearance may contribute to the unpredictability of clinical outcomes. We assessed genomic DNA from the plasma of 93 patients with high-risk primary or stage IV breast cancer, who received dose-intense paclitaxel, doxorubicin and cyclophosphamide. Eight polymorphisms in six genes associated with metabolism and transport of paclitaxel were analyzed using Pyrosequencing. We found no association between ABCB1, ABCG2, CYP1B1, CYP3A4, CYP3A5 and CYP2C8 genotypes and paclitaxel clearance. However, patients homozygous for the CYP1B1*3 allele had a significantly longer progression-free survival than patients with at least one Valine allele (P=0.037). This finding could reflect altered paclitaxel metabolism, however, the finding was independent of paclitaxel clearance. Alternatively, the role of CYP1B1 in estrogen metabolism may influence the risk of invasive or paclitaxel resistant breast cancer in patients carrying the CYP1B1*3 allele.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Neoplasias de la Mama
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Regulación Neoplásica de la Expresión Génica
/
Sistema Enzimático del Citocromo P-450
Límite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos