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. 2009 Dec 1;101(11):1817-23.
doi: 10.1038/sj.bjc.6605428.

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

H Jernström  1 , E Bågeman, C Rose, P-E Jönsson, C Ingvar
Affiliations

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

H Jernström et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
The figure shows that having at least one copy of the CYP2C8*3 allele conferred an increased risk for an early breast cancer-related event in tamoxifen-treated women with invasive ER-positive cancers (log rank 4.47; 1 df; P=0.034). HR 9.10 (95% CI 1.39-59.6; P=0.021), adjusted for invasive tumour size, age, PR, histological grade, axillary lymph node status, CYP2C8*4, CYP2C9*2, and CYP2C9*3. The number of patients at each time point is indicated.
See this image and copyright information in PMC

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