Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2.

ABSTRACT: Anastrozole is a widely prescribed aromatase inhibitor for the therapy of estrogen receptor positive (ER+) breast cancer. We performed a genome-wide association study (GWAS) for plasma anastrozole concentrations in 687 postmenopausal women with ER+ breast cancer. The top single-nucleotide polymorphism (SNP) signal mapped across SLC38A7 (rs11648166, P = 2.3E-08), which we showed to encode an anastrozole influx transporter. The second most significant signal (rs28845026, P = 5.4E-08) mapped near ALPPL2 and displayed epistasis with the SLC38A7 signal. Both of these SNPs were cis expression quantitative trait loci (eQTL)s for these genes, and patients homozygous for variant genotypes for both SNPs had the highest drug concentrations, the highest SLC38A7 expression, and the lowest ALPPL2 expres

SUBMITTER: Dudenkov TM 

PROVIDER: S-EPMC6612579 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature