CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients

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CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients

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Publication Article, peer reviewed scientific
Title CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients
Author(s) Jernström, Helena ; Bågeman, Erika ; Rose, Carsten ; Jönsson, Per-Ebbe ; Ingvar, Christian
Date 2009
English abstract
CYP2C8/9 polymorphisms may influence breast cancer-free survival after diagnosis due to their role in the metabolism of tamoxifen, paclitaxel, and other chemotherapy. cytochrome P450 (CYP)2C8/9 metabolise arachidonic acid to epoxyeicosatrienoic acids, which enhance migration and invasion in vitro and promote angiogenesis in vivo. We aimed to investigate the frequency of CYP2C8/9 polymorphisms in relation to breast tumour characteristics and disease-free survival. Methods: A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports. Results: Frequencies of CYP2C8/9 polymorphisms were similar to healthy European populations. Significantly less node involvement (P=0.002) and fewer PR+ tumours (P=0.012) were associated with CYP2C8*4. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/9*3/*1*/*2/*1 was the only factor associated with increased risk for early events in 297 tamoxifen-treated, ER-positive patients, adjusted HR 2.54 (95%CI 1.11–5.79). The effect appeared to be driven by CYP2C8*3, adjusted HR 8.56 (95%CI 1.53–51.1). Conclusion: Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients.
DOI http://dx.doi.org/10.1038/sj.bjc.6605428 (link to publisher's fulltext)
Publisher Nature Publishing Group
Host/Issue British Journal of Cancer;11
Volume 101
ISSN 0007-0920
Pages 1817-1823
Language eng (iso)
Subject(s) CYP2C8
CYP2C9
polymorphism
disease-free survival
tamoxifen
Medicine
Research Subject Categories::MEDICINE
Handle http://hdl.handle.net/2043/9602 (link to this page)

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