Sensorn Insee, Sirachainan Ekaphop, Chamnanphon Montri, Pasomsub Ekawat, Trachu Narumol, Supavilai Porntip, Sukasem Chonlaphat, Pinthong Darawan
Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2013 Aug 26;6:93-8. doi: 10.2147/PGPM.S44006. eCollection 2013.
Pharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug-metabolizing enzymes and transporters also play a role in tamoxifen metabolic pathways. The aim of this study is to investigate the impact of CYP3A4/5, ABCB1, and ABCC2 polymorphisms on the risk of recurrence in Thai patients who received tamoxifen adjuvant therapy.
Patients with early-stage breast cancer who received tamoxifen adjuvant therapy were recruited in this study. All six single-nucleotide polymorphisms (SNPs), including CYP3A41B (-392 A>G)/18(878 T>C), CYP3A53(6986 G>A), ABCB1 3435 C>T, ABCC21C(-24 C>T), and ABCC2 68231 A>G, were genotyped using real-time polymerase chain reaction assays. The impacts of genetic variants on disease-free survival (DFS) were analyzed using the Kaplan-Meier method and Cox regression analysis.
The ABCB1 3435 C>T was found to have the highest allele frequency among other variants; however, CYP3A4*1B/*18 could not be found in this study. Patients with heterozygous ABCB1 3435 CT genotype showed significantly shorter DFS than those with homozygous 3435 CC genotype (P = 0.041). In contrast, patients who carried homozygous 3435 TT genotype showed no difference in DFS from wild-type 3435 CC patients. Cox regression analysis showed that the relative risk of recurrence was increased by five times (P = 0.043; hazard ratio = 5.11; 95% confidence interval: 1.05-24.74) in those patients carrying ABCB1 3435 CT genotype compared to those with ABCB1 3435 CC.
ABCB1 3435 C>T is likely to have a clinically significant impact on recurrence risk in Thai patients with breast cancer who receive tamoxifen adjuvant therapy.
细胞色素P450（CYP）基因CYP2D6与他莫昔芬治疗结果的药物遗传学研究仍存在争议。除CYP2D6外，其他药物代谢酶和转运蛋白在他莫昔芬代谢途径中也发挥作用。本研究旨在探讨CYP3A4/5、ABCB1和ABCC2基因多态性对接受他莫昔芬辅助治疗的泰国患者复发风险的影响。
本研究招募了接受他莫昔芬辅助治疗的早期乳腺癌患者。使用实时聚合酶链反应分析法对包括CYP3A41B（-392 A>G）/18（878 T>C）、CYP3A53（6986 G>A）、ABCB1 3435 C>T、ABCC21C（-24 C>T）和ABCC2 68231 A>G在内的所有六个单核苷酸多态性（SNP）进行基因分型。使用Kaplan-Meier法和Cox回归分析来分析基因变异对无病生存期（DFS）的影响。
发现ABCB1 3435 C>T在其他变异中具有最高的等位基因频率；然而，本研究中未发现CYP3A4*1B/*18。ABCB1 3435 CT杂合基因型患者的DFS明显短于纯合3435 CC基因型患者（P = 0.041）。相比之下，携带纯合3435 TT基因型的患者与野生型3435 CC患者的DFS无差异。Cox回归分析显示，与ABCB1 3435 CC患者相比，携带ABCB1 3435 CT基因型的患者复发的相对风险增加了五倍（P = 0.043；风险比 = 5.11；95%置信区间：1.05 - 24.74）。
ABCB1 3435 C>T可能对接受他莫昔芬辅助治疗的泰国乳腺癌患者的复发风险产生临床显著影响。
