Onitilo Adedayo A, McCarty Catherine A, Wilke Russell A, Glurich Ingrid, Engel Jessica M, Flockhart David A, Nguyen Anne, Li Lang, Mi Deming, Skaar Todd C, Jin Yan
Department of Hematology/Oncology, Marshfield Clinic Weston Center, 3501 Cranberry Boulevard, Weston, WI 54476, USA.
Breast Cancer Res Treat. 2009 Jun;115(3):643-50. doi: 10.1007/s10549-008-0264-2. Epub 2008 Dec 12.
Thromboembolism is a serious complication of tamoxifen therapy in women with breast cancer. Banked DNA from tamoxifen-treated individuals with breast cancer from the Marshfield Clinic Personalized Medicine Research Project, a population-based DNA repository, was tested for association between incidence of tamoxifen-associated thromboembolic events (TTE) and single nucleotide polymorphisms encoding the estrogen receptors 1,2 (ESR1, ESR2) or drug metabolism enzymes cytochrome P450 2D6 (CYP2D6) and aromatase (CYP19). TTE were experienced by 16/220 subjects with risk association noted for XbaI (rs9340799) genotype and ESR1 Xbal/PvuII diplotype (rs9340799 and rs2234693) (hazard ratio 3.47, 95% CI 0.97-12.44, P = 0.035). Association persisted after adjusting for classical risk factors including age at diagnosis and body mass index at enrollment. Initial evidence of association between increased risk for TTE and ESR1 genotype and ESR1 diplotype is presented. Determination of estrogen receptor genotype may identify a subset of women at increased risk for thromboembolism with tamoxifen exposure.
血栓栓塞是乳腺癌女性患者接受他莫昔芬治疗时的一种严重并发症。来自马什菲尔德诊所个性化医学研究项目（一个基于人群的DNA储存库）中接受他莫昔芬治疗的乳腺癌患者的存档DNA，被用于检测他莫昔芬相关血栓栓塞事件（TTE）的发生率与编码雌激素受体1、2（ESR1、ESR2）或药物代谢酶细胞色素P450 2D6（CYP2D6）和芳香化酶（CYP19）的单核苷酸多态性之间的关联。16/220名受试者经历了TTE，发现XbaI（rs9340799）基因型和ESR1 Xbal/PvuII双倍型（rs9340799和rs2234693）存在风险关联（风险比3.47，95%可信区间0.97 - 12.44，P = 0.035）。在对包括诊断时年龄和入组时体重指数等经典风险因素进行校正后，这种关联仍然存在。本文展示了TTE风险增加与ESR1基因型和ESR1双倍型之间关联的初步证据。雌激素受体基因型的测定可能会识别出一部分因接触他莫昔芬而发生血栓栓塞风险增加的女性。
