Variation of CYP2D6 genotype between Caucasian and Asian population and inconsistency of serum endox-ifen concentration and phenotype of CYP2D6 in Chinese breast cancer patients / 实用医学杂志

ABSTRACT

Objective To conduct a prospective phase Ⅱ clinical study to explore the distribution of CYP2D6 gene polymorphism in Chinese population and its relationship with the metabolism of tamoxifen in early-stage hormonal receptor-positive breast cancer. Methods CYP2D6 genotype was tested by Sanger sequencing using the ABI 3500 Genetic Analyzer. Plasma concentrations of tamoxifen and endoxifen were measured using the HPLC-MS/MS(API 2000)assay. We downloaded the data of CYP2D6 allele from the CPIP database. Results In Chi-nese patients,the most common alleles were CYP2D6*1,*2,and *10;the predominant diplotypes were *1/*10 (38.3%)and*10/*10(18.8%). The distribution of metabolic phenotype,plasma concentration of endoxifen,and endoxifentamoxifen plasma concentration ratio were inconsistent between the normal metabolic phenotype(EM) and the intermediate phenotype(IM)under different CYP2D6 activity prediction criteria.The differences in the ratios and endoxifen plasma concentrations were statistically significant between the three groups by cluster analysis. Conclusions The CYP2D6 genotype distribution in Chinese population is different from that in the Western popu-lation. There is considerable variation of serum endoxifen concentration in Chinese breast cancer patients possess-ing the phenotype previously known as the intermediate active metabolizers of CYP2D6. Therefore,in the current era of precision medicine,the standard CYP2D6 genotype-phenotype classification system cannot properly stratify the Chinese population with different levels of endoxifen plasma concentration.