CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients.
(2009) In British Journal of Cancer 101(11). p.1817-1823- Abstract
- BACKGROUND: 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... (More)
- BACKGROUND: 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1511601
- author
- Jernström, Helena LU ; Bågeman, Erika LU ; Rose, Carsten LU ; Jönsson, Per-Ebbe LU and Ingvar, Christian LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Cancer
- volume
- 101
- issue
- 11
- pages
- 1817 - 1823
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000272188500003
- pmid:19935798
- scopus:70549085147
- pmid:19935798
- ISSN
- 1532-1827
- DOI
- 10.1038/sj.bjc.6605428
- language
- English
- LU publication?
- yes
- id
- ef1582a3-6ce1-41d6-bdb4-6aa9aaa1cb99 (old id 1511601)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19935798?dopt=Abstract
- date added to LUP
- 2016-04-04 08:12:12
- date last changed
- 2022-04-23 17:11:02
@article{ef1582a3-6ce1-41d6-bdb4-6aa9aaa1cb99,
abstract = {{BACKGROUND: 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.}},
author = {{Jernström, Helena and Bågeman, Erika and Rose, Carsten and Jönsson, Per-Ebbe and Ingvar, Christian}},
issn = {{1532-1827}},
language = {{eng}},
number = {{11}},
pages = {{1817--1823}},
publisher = {{Nature Publishing Group}},
series = {{British Journal of Cancer}},
title = {{CYP2C8 and CYP2C9 polymorphisms in relation to tumour characteristics and early breast cancer related events among 652 breast cancer patients.}},
url = {{http://dx.doi.org/10.1038/sj.bjc.6605428}},
doi = {{10.1038/sj.bjc.6605428}},
volume = {{101}},
year = {{2009}},
}