CYP2D6基因多态性与他莫昔芬及4-羟基他莫昔芬血清浓度的相关性研究  

Clinical analysis of CYP2D6 gene polymorphism with serum concentration of tamoxifen and 4-Hydroxytamoxifen

作　　者：田超[1] 杨义[2] 李卉[1] 

机构地区：[1]四川省肿瘤医院乳腺科,四川成都610041 [2]成都中医药大学管理学院,四川成都610041

出　　处：《四川医学》2014年第1期4-6,共3页Sichuan Medical Journal

基　　金：四川省卫生厅科研项目(编号:110265)

摘　　要：目的 探讨CYP2D6基因多态性与乳腺癌患者他莫昔芬（TAM）及其活性代谢产物4-羟基他莫昔芬（4-OH-TAM）血清浓度的相关性.方法 收集2008年1月~2010年10月期间200例服用TAM的乳腺癌患者的口腔粘膜及血清,采用Real-time RT-PC法检测CYP2D6＊10基因多态性,采用液相色谱-质谱方法 （LC-MS）测定患者体内TAM及其活性代谢物4-OH-TAM的的血清浓度.结果 200例乳腺癌中检测到CYP2D6＊10/＊10纯合子94例（47%）,CYP2D6 wt/wt野生型48例（24%）,CYP2D6 wt/＊10杂合型58例（29%）.CYP2D6 wt/wt野生型和wt/＊10杂合型两组4-OH-TAM的血清浓度都明显高于＊10/＊10纯合型（P〈0.05）,各基因型之间TAM血清浓度值差异无统计学意义（P〉0.05）.结论 乳腺癌患者CYP2D6＊10/＊10基因型影响他莫昔芬的体内代谢过程,与疗效相关,服用TAM前均应推荐检测CYP2D6＊10/＊10基因型.Objective To explore the relationship between CYP2D6 gene polymorphism with serum concentration of tamoxifen （TAM） and its active metabolites （4-hydroxy tamoxifen, 4-0H-TAM）. Methods The oral mucosas and serum were obtained from 200 breast cancer patients received oral administration of TAM. Real-time RT-PCR was used to determine CYP2D6 ^＊10 gene polymorphism. Serum TAM and 4-0H-TAM concentration of patients were determined by using liquid chromatography-trap mass spectrometry （LC-MS）. Results Of 200 cases of breast cancer patients, CYP2D6 ^＊ 10/ ^＊ 10 homozygotes were found in 94 cases （47% ）, CYP2D6 wtlwt wild type in 48 cases （24%） and CYP2D6 wtI ＊ 10 heterozygote in 58 cases （29% ）. The concentration of serum 4-0H-TAM in patients with CYP2D6 wtlwt wild type and wt/ ^＊ 10 heterozygote was significantly higher than that in patients with CYP2D6 ^＊10/^＊ 10 homozygote （P 〈 0.05）, however, serum TAM concentration in patients with different genotypes was not statistically different （P 〉 0. 05）. Conclusion CYP2D6 ^＊ 10/ ^＊ 10 genotype is related to curative effect of TAM of breast cancer patients, indicating that CYP2D6 ^＊ 10/^＊ 10 genotype should be routinely determined before TAM administration.

关 键 词：乳腺癌 他莫昔芬 CYP2D6 4-羟基他莫昔芬 

分 类 号：R737.9[医药卫生—肿瘤]