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

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 ¼ 0.002) and fewer PR þ tumours (P ¼ 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 tamoxifentreated patients.

Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status

“…It is therefore plausible that tamoxifen response is influenced by the CYP1A2*1F genotype and coffee intake and that any effect of coffee may be dependent on the CYP1A2*1F genotype. Similarly, CYP2C8*3 genotypes have previously been shown to be associated with an increased risk for early events in a subset of tamoxifen-treated patients from the present cohort [21]. Tamoxifen response may therefore also be influenced by CYP2C8 genotype and coffee intake.…”

“…CYP2C8/9 also contributes to the metabolism of caffeine [17] and tamoxifen [16]. CYP2C8*3 genotypes, which may influence CYP2C8 enzyme metabolic activity [38], have previously been associated with a higher risk for early breast cancer events in tamoxifentreated patients, in a subset of the present cohort [21]. Intake of caffeinated coffee may thus result in increased activation of tamoxifen via CYP1A2 or CYP2C8/9, a hypothesis consistent with our finding of fewer early events in tamoxifen-treated patients with ER+ tumors and moderate to high coffee consumption.…”

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

“…The relationship between breast cancer and the CYP gene family was recently reported, including CYP1B1 (Economopoulos and Sergentanis, 2010;Ozbek et al, 2010), CYP2J2 (Jiang et al, 2007(Jiang et al, , 2009), CYP2D6 (Stingl et al, 2010;González-Tejera et al, 2010;Thompson et al, 2011), CYP2C8 (Knüpfer et al, 2004;Dixit, et al, 2007;Jernström et al, 2009), CYP2C9 (Ekhart et al, 2008;Jernström et al, 2009) and CYP2C19 (Justenhoven et al, 2009;Ruiter et al, 2010;Goetz and Suman, 2010). Several studies have reported different conclusions for the relationship with CYP2C19.…”

Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort

“…After a written informed consent was signed, a questionnaire regarding lifestyle, reproductive factors, and medications was completed (10). Blood samples were taken and body measurements, including breast volume, were recorded by a research nurse.…”