Pharmacogenomic eQTL mediated by androgen receptor modulators

Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen recepto alpha (ERa). The androgen receptor (AR) is also expressed in the vast majority (80-90%) of ERa-positive tumors. However, AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies.We performed a genome-wide study to identify genetic context-dependent AR signaling induced by either AR agonist (dihydrotestosterone [DHT]), or AR antagonist (enzalutamide [Enz]), known as pharmacogenomic expression quantitative expression loci (PGx-eQTLs), utilizing a previously well characterized lymphoblastic cell line panel. Clinical relevance of identified SNPs-gene pairs were examined by examining their association with breast cancer phenotypes from three genome-wide association (GWAS) studies we have published and from GWAS catalog.