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CYP2D64 polymorphism affects breast cancer survival in tamoxifen users
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Journal Article
CYP2D64 polymorphism affects breast cancer survival in tamoxifen users
2009
Overview
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.
Publisher
Boston : Springer US,Springer US,Springer,Springer Nature B.V,Springer Verlag
Subject
/ Alleles
/ Antineoplastic Agents, Hormonal - pharmacokinetics
/ Antineoplastic Agents, Hormonal - therapeutic use
/ Biological and medical sciences
/ Biotransformation - genetics
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - enzymology
/ Cytochrome P-450 CYP2D6 - deficiency
/ Cytochrome P-450 CYP2D6 - genetics
/ Cytochrome P-450 CYP2D6 - physiology
/ Cytochrome P-450 CYP2D6 Inhibitors
/ Female
/ Genotype
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Medicine
/ Oncology
/ Polymorphism, Single Nucleotide
/ Tamoxifen - analogs & derivatives
/ Tamoxifen - pharmacokinetics
/ Tumors
