Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-10

AUTHORS

S Marsh, G Somlo, X Li, P Frankel, C R King, W D Shannon, H L McLeod, T W Synold

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. More... »

PAGES

6500434

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.tpj.6500434

DOI

http://dx.doi.org/10.1038/sj.tpj.6500434

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026106232

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17224914


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