title: Laboratory testing of CYP2D6 alleles in relation to tamoxifen therapy.
abstract: Tamoxifen, a widely prescribed drug for the treatment and prevention of breast cancer, is metabolized to more potent metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme. Variants in the CYP2D6 gene can cause patients to be either intermediate or poor metabolizers, thereby rendering tamoxifen treatment less effective. Testing for CYP2D6 gene variants is available in Clinical Laboratory Improvement Amendments-certified clinical laboratories; however, the biological complexity of the variants makes result interpretation and phenotype prediction challenging. This article describes the clinical significance of variants as well as important analytical, interpretative, and reporting issues. It is designed to be a guideline for clinical laboratory professionals in performing tests and interpreting results with respect to CYP2D6 genetic variants.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Molecular Genetics, ARUP Laboratories, Salt Lake City, Utah, USA. lyone@aruplab.com
authors.forename: Elaine
authors.initials: E
authors.lastname: Lyon
authors.forename: Julie
authors.initials: J
authors.lastname: Gastier Foster
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Pratt
authors.forename: Kristen
authors.initials: K
authors.lastname: Reynolds
authors.forename: M Fernanda
authors.initials: MF
authors.lastname: Sábato
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Scott
authors.forename: Patrik
authors.initials: P
authors.lastname: Vitazka
mesh_terms: D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D060005:Genotyping Techniques; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen; D019389:Cytochrome P-450 CYP2D6