Correlation between polymorphism of CYP2D6 gene with effect of tamoxifen in patients with breast cancer
10.3760/cma.j.issn.1007-631X.2014.04.016
- VernacularTitle:CYP2D6多态性与乳腺癌患者他莫昔芬疗效的相关性
- Author:
Chao TIAN
;
Yi YANG
;
Hui LI
- Publication Type:Journal Article
- Keywords:
Breast neoplasms;
Tamoxifen;
Polymorphism,single nucleotide;
Prognosis;
CYP2D6
- From:
Chinese Journal of General Surgery
2014;29(4):299-302
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the correlation of CYP2D6 gene polymorphism and serum tamoxifen (TAM) and its active metabolites (4-hydroxy tamoxifen,4-OH-TAM) in terms of prognosis of breast cancer patients.Methods The oral mucosas and serum were obtained from 200 breast cancer patients receiving oral TAM from Jan 2008 to Oct 2010.Real-time RT-PCR was used to determine CYP2D6* 10 gene polymorphism.The relationship between CYP2D6* 10 gene polymorphism and clinicopathological features and prognosis was assessed by Chi-square test and Cox proportional model.Serum TAM and 4-OH-TAM concentration were determined by liquid chromatography-trap mass spectrometry (LC-MS).Results Of 200 breast cancer patients,CYP2D6 * 10/* 10 homozygotes were found in 94 cases (47％),CYP2D6 wt/wt wild type in 48 cases (24％) and CYP2D6 wt/* 10 heterozygote in 58 cases (29％).The concentration of serum 4-OH-TAM in patients with CYP2D6 wt/wt wild type and wt/* 10 heterozygote was significantly higher than that in patients with CYP2D6 * 10/ * 10 homozygote (F =4.31,P =0.01).CYP2D6 gene polymorphism was not related to clinicopathological features (P ＞ 0.05).Logrank test showed that patient's disease-free survival with mutational CYP2D6 (mean,47.2 months) was significantly shorter than that in patients without mutational CYP2D6 (mean,51.2 months) (P =0.018).Cox proportional model showed that CYP2D6 genotype was related to disease-free survival (HR =2.755,95％CI:1.230 ～6.173,P =0.014).Conclusions CYP2D6 *10/* 10 genotype is related to curative effect of TAM on breast cancer patients,detection of CYP2D6 * 10/* 10 genotype helps improve the choice of TAM therapy.
