Non-CYP2D6 Variants Selected by a GWAS Improve the Prediction of Impaired Tamoxifen Metabolism in Patients with Breast Cancer.

ABSTRACT: A certain minimum plasma concentration of (Z)-endoxifen is presumably required for breast cancer patients to benefit from tamoxifen therapy. In this study, we searched for DNA variants that could aid in the prediction of risk for insufficient (Z)-endoxifen exposure. A metabolic ratio (MR) corresponding to the (Z)-endoxifen efficacy threshold level was adopted as a cutoff value for a genome-wide association study comprised of 287 breast cancer patients. Multivariate regression was used to preselect variables exhibiting an independent impact on the MR and develop models to predict below-threshold MR values. In total, 15 single-nucleotide polymorphisms (SNPs) were significantly associated with below-threshold MR values. The strongest association was with rs8138080 (WBP

SUBMITTER: Hennig EE 

PROVIDER: S-EPMC6722498 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature