The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users

被引：91

作者：

Bijl, Monique J. ^{[1
,2
]}

van Schaik, Ron H. N. ^{[3
]}

Lammers, Laureen A. ^{[2
]}

Hofman, Albert ^{[1
]}

Vulto, Arnold G. ^{[2
]}

van Gelder, Teun ^{[2
,4
]}

Stricker, Bruno H. Ch. ^{[1
,4
,5
]}

Visser, Loes E. ^{[1
,2
]}

机构：

[1] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Dept Hosp Pharm, NL-3000 CA Rotterdam, Netherlands

[3] Erasmus MC, Dept Clin Chem, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands

[5] Inspectorate Hlth Care, Drug Safety Unit, NL-2500 BC The Hague, Netherlands

来源：

BREAST CANCER RESEARCH AND TREATMENT | 2009年 / 118卷 / 01期

关键词：

CYP2D6*4; Polymorphism; Tamoxifen; Breast cancer; ALLELE FREQUENCY; CYP2D6; GENOTYPE; METABOLISM; THERAPY; BIOTRANSFORMATION; OPTIMIZATION; VARIANTS; DISEASE; ENZYMES;

D O I：

10.1007/s10549-008-0272-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. In this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Breast cancer mortality was significantly increased in patients with the *4/*4 genotype (HR = 4.1, CI 95% 1.1-15.9, P = 0.041) compared to wild type patients. The breast cancer mortality increased with a hazard ratio of 2.0 (CI 95% 1.1-3.4, P = 0.015) with each additional variant allele. No increased risk of all-cause mortality or all-cancer mortality was found in tamoxifen users carrying a CYP2D6*4 allele. The risk of breast cancer mortality is increased in tamoxifen users with decreased CYP2D6 activity, consistent with the model in which endoxifen formation is dependent on CYP2D6 activity.

引用

页码：125 / 130

页数：6

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