In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 106, No. 1 ( 2019-07), p. 219-227
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 SLC 38A7 (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 ALPPL 2 and displayed epistasis with the SLC 38A7 signal. Both of these SNP s were cis expression quantitative trait loci ( eQTL )s for these genes, and patients homozygous for variant genotypes for both SNP s had the highest drug concentrations, the highest SLC 38A7 expression, and the lowest ALPPL 2 expression. In summary, our GWAS identified a novel gene encoding an anastrozole transporter, SLC 38A7 , as well as epistatic interaction between SNP s in that gene and SNP s near ALPPL 2 that influenced both the expression of the transporter and anastrozole plasma concentrations.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
DOI:
10.1002/cpt.2019.106.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2040184-X
SSG:
15,3
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