Genome-wide discovery of genetic variants affecting tamoxifen sensitivity and their clinical and functional validation.

ABSTRACT:

Background

Beyond estrogen receptor (ER), there are no validated predictors for tamoxifen (TAM) efficacy and toxicity. We utilized a genome-wide cell-based model to comprehensively evaluate genetic variants for their contribution to cellular sensitivity to TAM.

Design

Our discovery model incorporates multidimensional datasets, including genome-wide genotype, gene expression, and endoxifen-induced cellular growth inhibition in the International HapMap lymphoblastoid cell lines (LCLs). Genome-wide findings were further evaluated in NCI60 cancer cell lines. Gene knock-down experiments were performed in four breast cancer cell lines. Genetic variants identified in the cell-based model were examined in 245 Caucasian breast cancer patients who underwent TAM treatment.

Results</

SUBMITTER: Weng L 

PROVIDER: S-EPMC3690911 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature