Department of Epidemiology, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Pharmacogenomics. 2010 Oct;11(10):1367-75. doi: 10.2217/pgs.10.112.
Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen.
MATERIALS & METHODS: In the prospective population based Rotterdam study, the association between CYP2C19*2 carriers and breast cancer mortality was studied among 80 incident users of tamoxifen. Survival was analyzed with life tables and Cox regression analysis, with drug exposure as a time-dependent variable. Adjustments were made for calendar time, average tamoxifen dose, age, the indication for tamoxifen, CYP2D6 genotype and concomitant use of CYP2C19 inhibitors or inducers.
In patients on tamoxifen, CYP2C19*2 carriers were associated with a significantly longer breast cancer survival rate than patients with the wild-type (hazard ratio 0.26, 95%CI: 0.08-0.87).
This study suggests that CYP2C19 genotype may possibly be a predictive factor for survival in breast cancer patients using tamoxifen.
CYP2C19 基因的变异等位基因最近与接受他莫昔芬治疗的乳腺癌患者的生存有关。CYP2C19 是参与他莫昔芬代谢为活性代谢物的酶之一。我们研究了假设，即缺乏酶活性的 CYP2C19*2 和 *3 变体与使用他莫昔芬的患者乳腺癌死亡率增加有关。
在前瞻性基于人群的鹿特丹研究中，研究了 80 例新使用他莫昔芬的患者中 CYP2C19*2 携带者与乳腺癌死亡率之间的关系。使用寿命表和 Cox 回归分析来分析生存情况，药物暴露作为时间依赖性变量。调整了日历时间、平均他莫昔芬剂量、年龄、他莫昔芬的适应证、CYP2D6 基因型以及 CYP2C19 抑制剂或诱导剂的同时使用。
在接受他莫昔芬治疗的患者中，CYP2C19*2 携带者的乳腺癌生存率明显长于野生型患者（风险比 0.26，95%CI：0.08-0.87）。
这项研究表明，CYP2C19 基因型可能是使用他莫昔芬的乳腺癌患者生存的预测因素。
