Jernström H, Bågeman E, Rose C, Jönsson P-E, Ingvar C
Department of Oncology, Clinical Sciences, Lund University, Barngatan 2B, Lund SE-221 85, Sweden.
Br J Cancer. 2009 Dec 1;101(11):1817-23. doi: 10.1038/sj.bjc.6605428.
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.
A prospective series of 652 breast cancer patients from southern Sweden was genotyped for CYP2C83, CYP2C84, CYP2C92, and CYP2C93. Blood samples and questionnaires were obtained pre- and postoperatively. Clinical information and tumour characteristics were obtained from patients' charts and pathology reports.
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 CYP2C84. Median follow-up was 25 months and 52 breast cancer-related events were reported. In a multivariate model, CYP2C8/93/1/*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 CYP2C83, adjusted HR 8.56 (95%CI 1.53-51.1).
Polymorphic variants of CYP2C8/9 may influence breast tumour characteristics and disease-free survival in tamoxifen-treated patients.
细胞色素P450（CYP）2C8/9基因多态性可能因其在他莫昔芬、紫杉醇及其他化疗药物代谢中的作用而影响乳腺癌诊断后的无瘤生存期。CYP2C8/9可将花生四烯酸代谢为环氧二十碳三烯酸，后者在体外可增强迁移和侵袭能力，在体内可促进血管生成。我们旨在研究CYP2C8/9基因多态性的频率与乳腺肿瘤特征及无病生存期的关系。
对瑞典南部652例乳腺癌患者进行前瞻性研究，检测其CYP2C83、CYP2C84、CYP2C92和CYP2C93基因分型。术前和术后采集血样并进行问卷调查。临床信息和肿瘤特征来自患者病历及病理报告。
CYP2C8/9基因多态性频率与健康欧洲人群相似。CYP2C84与淋巴结受累显著减少（P = 0.002）及孕激素受体（PR）阳性肿瘤较少（P = 0.012）相关。中位随访时间为25个月，报告了52例乳腺癌相关事件。在多变量模型中，CYP2C8/93/1/*2/1是297例接受他莫昔芬治疗的雌激素受体（ER）阳性患者早期事件风险增加的唯一相关因素，校正后风险比（HR）为2.54（95%置信区间[CI] 1.11 - 5.79）。该效应似乎由CYP2C83驱动，校正后HR为8.56（95%CI 1.53 - 51.1）。
CYP至8/9基因多态性变异可能影响接受他莫昔芬治疗患者的乳腺肿瘤特征及无病生存期。
