Evidence map›Paper›PMID 30648747›Full record

ArticleClinical pharmacology and therapeutics2019

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

Tanda M Dudenkov, Duan Liu, Junmei Cairns, Sandhya Devarajan, Yongxian Zhuang, James N Ingle, Aman U Buzdar, Mark E Robson, Michiaki Kubo, Anthony Batzler and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Clinical pharmacology and therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Effects ofPharmacogenomics · 2023
    Article
  3. Review
  4. Genomewide Association Studies in Pharmacogenomics.Clinical pharmacology and therapeutics · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 2 countries.

Tanda M DudenkovDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Duan LiuDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0003-1065-246X
Junmei CairnsDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-3941-4564
Sandhya DevarajanDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Yongxian ZhuangDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
James N IngleDivision of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0003-1257-7731
Aman U BuzdarDepartment of Breast Oncology, MD Anderson Cancer Center, Houston, Texas, USA.
Mark E RobsonBreast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Michiaki KuboRIKEN Center for Integrative Medical Sciences, Yokohama City, Japan.
Anthony BatzlerDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Poulami BarmanDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Gregory D JenkinsDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Erin E CarlsonDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Matthew P GoetzDivision of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Donald W NorthfeltDivision of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
Alvaro Moreno-AspitiaDivision of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, USA.
Zeruesenay DestaDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Joel M ReidDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Krishna R KalariDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Liewei WangDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Richard M WeinshilboumDivision of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-4911-7985
Mayo Clinic · USMayo Clinic in Florida · USIndiana University School of MedicineJacksonville College · USMayo Clinic in Arizona · USMemorial Sloan Kettering Cancer Center · USRIKEN Center for Integrative Medical Sciences · JPThe University of Texas MD Anderson Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Pharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8M
TRAININGU54GM114838 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI HAN, JIAWEI, SINHA, SAURABH · 2014 to 2017
$10.8M
INHERITED VARIATIONS IN DRUG-METABOLIZING ENZYMESR01GM028157 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 1985 to 2019
$6.9M
Medical Scientist Traning Program at Mayo ClinicT32GM065841 · NIGMS · MAYO CLINIC ROCHESTER · PI KAUFMANN, SCOTT H, SCHIMMENTI, LISA A · 2003 to 2022
$5.8M
Pharmacogenomic regulation of CYP transcription by TSPYL genesR01GM125633 · NIGMS · MAYO CLINIC ROCHESTER · PI WANG, LIEWEI · 2018 to 2021
$1.2M
NCI NIH HHS N01 CA015083NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA116201NIGMS NIH HHS R01 GM028157NIGMS NIH HHS R01 GM125633NIGMS NIH HHS T32 GM065841NIGMS NIH HHS U19 GM061388NIGMS NIH HHS U54 GM114838
6 · The paper itself

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 expression. In summary, our GWAS identified a novel gene encoding an anastrozole transporter, SLC38A7, as well as epistatic interaction between SNPs in that gene and SNPs near ALPPL2 that influenced both the expression of the transporter and anastrozole plasma concentrations.

Indexed as

Alkaline PhosphataseAnastrozoleAromatase InhibitorsBreast NeoplasmsChromosomes, Human, Pair 16Chromosomes, Human, Pair 2Epistasis, GeneticFemaleGenome-Wide Association StudyGenotypeGPI-Linked ProteinsHumansPolymorphism, Single NucleotidePostmenopauseReceptors, EstrogenAlkaline PhosphataseALPG protein, humanAnastrozoleAromatase InhibitorsGPI-Linked ProteinsReceptors, Estrogen

Identifiers

PMID30648747
PMCPMC6612579
OpenAlexW2910250809

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.