Mayo Clinic, Rochester, MN 55905, USA.
Pharmacogenomics. 2011 Nov;12(11):1535-43. doi: 10.2217/pgs.11.97. Epub 2011 Oct 3.
Tamoxifen biotransformation to endoxifen, a potent antiestrogen, is catalyzed by CYP2D6. In addition, CYP2C19 and SULT1A1 have also been implicated in the metabolism of tamoxifen. We sought to evaluate the importance of SULT1A1 copy number and CYP2C19*17 on disease-free survival (DFS) in postmenopausal women randomized to tamoxifen monotherapy in North Central Cancer Treatment Group 89-30-52 from January 1991 to April 1995.
MATERIALS & METHODS: We extracted DNA from paraffin-embedded tumors and determined tumor SULT1A1 copy number and CYP2C1917 genotype. The association of genotype with DFS was determined using the log-rank test. Multivariate cox modeling was performed using traditional prognostic factors, as well as CYP2D6 genotype. SULT1A1 copy number and CYP2C1917 genotype was determined in 190 out of 256 patients (95% Caucasian).
The median follow-up for living patients was 14 years. DFS did not differ according to SULT1A1 copy number (p = 0.482) or CYP2C1917 genotype (p = 0.667). Neither SULT1A1 copy number or CYP2C1917 genotype was associated with disease recurrence in this cohort.
Future studies are needed to identify whether other genetic and environmental factors which affect tamoxifen metabolism are associated with tamoxifen clinical outcomes.
他莫昔芬向强效抗雌激素(endoxifen)的生物转化由 CYP2D6 催化。此外，CYP2C19 和 SULT1A1 也被认为参与了他莫昔芬的代谢。我们试图评估 SULT1A1 拷贝数和 CYP2C19*17 对 1991 年 1 月至 1995 年 4 月期间接受他莫昔芬单药治疗的绝经后妇女无病生存（DFS）的重要性。
我们从石蜡包埋的肿瘤中提取 DNA，并确定肿瘤 SULT1A1 拷贝数和 CYP2C1917 基因型。使用对数秩检验确定基因型与 DFS 的关联。使用传统的预后因素以及 CYP2D6 基因型进行多变量 Cox 建模。在 256 名患者中的 190 名（95%为白种人）中确定了 SULT1A1 拷贝数和 CYP2C1917 基因型。
存活患者的中位随访时间为 14 年。DFS 与 SULT1A1 拷贝数（p = 0.482）或 CYP2C1917 基因型（p = 0.667）无关。在该队列中，SULT1A1 拷贝数或 CYP2C1917 基因型均与疾病复发无关。
需要进一步的研究来确定是否其他影响他莫昔芬代谢的遗传和环境因素与他莫昔芬的临床结局相关。
