激素受体阳性乳腺癌患者CYP2D6基因多态性及拷贝数变异与他莫昔芬治疗预后的相关性研究

Correlation between the difference of CYP2D6 gene polymorphism and copy number variation and prognosis of tamoxifen therapy in patients with hormone receptor positive breast cancer

目的探讨激素受体阳性乳腺癌患者CYP2D6基因多态拷贝数变异与他莫昔芬治疗预后的相关性。方法选取接受手术治疗的激素受体阳性乳腺癌患者253例,采用Taq Man实时荧光定量PCR技术和Accu CopyTM多重基因拷贝数检测技术进行CYP2D6基因多态性及拷贝数变异检测。结果 97.6%(247/253)的患者检测到了CYP2D6等位基因多态性或拷贝数变异情况,CYP2D6基因多拷贝的发生率为14.3%(36/253),其中功能型等位基因(*1、*2)多拷贝表达发生率约2.8%(7/253)。UM型患者7例均为CYP2D6功能等位基因*1、*2多拷贝所致,均在无复发转移组检测到,而复发转移组未发现,两组差异有统计学意义(P<0.05)。结论存在功能等位基因*1、*2多拷贝的乳腺癌超快代谢型患者,在服用他莫昔芬治疗后效果更好,为他莫昔芬个体化治疗的进一步研究提供了一定依据。

Objective To investigate the polymorphism and copy number variation of CYP2D6 gene in different prognostic hormone receptor positive breast cancer patients.Methods 253 patients with hormone receptor-positive breast cancer were selected.TaqMan real-time fluorescence quantitative PCR technology and AccuCopy TM multigene copy number detection technology were used to detect CYP2D6 gene polymorphism and copy number variation detection.Results Patients with 97.6%(247/253)detected the CYP2D6 allele polymorphism or copy number variation.The incidence of multiple copies of CYP2D6 gene was 14.3%(36/253),and the rate of multiple copies of functional allele(*1,*2)was about 2.8%(7/253).7 patients of UM were all caused by multiple copies of CYP2D6 function allele*1 and*2.They were detected in the group without recurrence and metastasis,while no recurrence was found in the recurrence and metastasis group.The difference between the two groups was statistically significant.Conclusion The patients with breast cancer who have the functional alleles*1,*2 and multiple copies of breast cancer have better effect after tamoxifen treatment,which provides a basis for further research on the individualized treatment of tamoxifen.