乳腺癌患者CYP2D6多态性与Endoxifen血药浓度的相关性分析  

Association between CYP2D6 polymorphism and plasma concentration of Endoxifen in breast cancer patients

作　　者：杨汐[1] 罗波[2] 吴斌[1] 

机构地区：[1]泸州医学院附属医院乳腺外科,四川泸州646000 [2]泸州医学院生物化学教研室,四川泸州646000

出　　处：《中华肿瘤防治杂志》2013年第12期922-925,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：四川省教育厅重点科研(11ZA236)

摘　　要：目的:研究乳腺癌术后服用他莫昔芬(TAM)辅助治疗绝经前、雌激素受体(ER)阳性患者CYP2D6基因多态性与TAM活性代谢产物Endoxifen血药浓度的相关性,及其与TAM不良反应发生的相关性。方法:57例乳腺癌术后经TAM辅助治疗的患者(绝经前、ER阳性),采用Tetra-primer ARMS PCR检测其CYP2D6基因型,采用LC-MS/MS测定所有患者体内TAM及其活性代谢产物Endoxifen的血药浓度;根据患者自述标记存在治疗不良反应的个体。结果:CYP2D6*10/*10型和*1/*10型受试者体内Endoxifen的血药浓度值分别为(23.55±4.01)和(25.90±3.93)ng/mL,均显著低于*1/*1型受试者(34.82±5.95)ng/mL,差异有统计学意义,P<0.01;但*10/*10型和*1/*10型之间Endoxifen的浓度值差异无统计学意义,P>0.05。CYP2D6*1/*1型组自述无任何不良反应的比例(22.2%)低于突变组(62.5%),且差异有统计学意义,P<0.05。结论:CYP2D6基因多态性与Endoxifen血药浓度的差异及TAM治疗不良反应的发生有关;根据CYP2D6基因型,可指导绝经前、ER阳性乳腺癌患者术后的TAM个体化用药。OBJECTIVE： To study the association between polymorphism of CYP2D6 and plasma concentration of Endoxifen （an activity metabolite of tamoxifen） in premenopausal ER-positive breast cancer patients receiving adjuvant tamoxifen（TAM）treatment and explore the association between the polymorphism of CYP2D6 and the occurrence of drug side effects in the same participants. METHODS： Tetra-primer ARMS PCR was used to detect the genotypes of CYP2D6 in 57 participants,liquid chromatography tandem mass spectrometry（LC-MS/MS）was used to detect the plasma concen- trations of TAM and its activitive metabolite Endoxifen,and the patients who experiencing the side effects of TAM from current medication was marked. RESULTS： The plasma concentration of Endoxifen in group ＊ 10/＊ 10 （23. 55 ±4.01） ng/mL and group ＊ 1/＊ 10（25.90±3.93） ng/mL were significantly lower than that in group ＊ 1/＊ 1（34.82±5.95） ng/mL（P〈0.01）. There was no significant difference between group ＊ 10/＊ 10 and group ＊ 1/＊ 10（P〉0.05）. The occurrence of self-reported TAM side effects in group ＊ 1/＊ 1 （22.2 % ）was less than that in mutant groups（62.5 % ）, the difference was significant（P〈0.05）. CONCLUSIONS： The plasma concentration of Endoxifen and the occurrence of TAM-related side effects are relevant to CYP2D6 polymorphism. According to the CYP2D6 genotype,it is feasible to guide the rational application of personalized medicine in the treatment of TAM for premenopausal ER-positive breast cancer patients after surgery.

关 键 词：CYP2D6 基因多态性 ENDOXIFEN 他莫昔芬 内分泌治疗 乳腺肿瘤 

分 类 号：R737.9[医药卫生—肿瘤]