Trial reportMolecular endocrinology (Baltimore, Md.)2013
TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression.
Trial report in Molecular endocrinology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Modulation of genetic associations with serum urate levels by body-mass-index in humans.PloS one · 2015Pooled it
- Genetic Variation in Steroid and Xenobiotic Metabolizing Pathways and Enterolactone Excretion Before and After Flaxseed Intervention in African American and European American Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2019Trial
- Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics.Molecular endocrinology (Baltimore, Md.) · 2014Trial
- Thiopurine pharmacogenomics: association of SNPs with clinical response and functional validation of candidate genes.Pharmacogenomics · 2014Trial
- TSPY-like 2, Beyond the Histone Chaperone Role.Biomolecules · 2026Review
- Genome-wide association and expression quantitative trait loci in cattle reveals common genes regulating mammalian fertility.Communications biology · 2024Article
- The effect of genetic variants in the transcription factor TSPYL family on the CYP3A4 mediated cyclosporine metabolism in kidney transplant patients.Clinical and translational science · 2024Article
- Cancer Metastasis Prediction and Genomic Biomarker Identification through Machine Learning and eXplainable Artificial Intelligence in Breast Cancer Research.Diagnostics (Basel, Switzerland) · 2023Article
- Article
- Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma.Oxidative medicine and cellular longevity · 2022Article
- Testis- specific Y-encoded- like protein 1 and cholesterol metabolism: Regulation ofFrontiers in pharmacology · 2022Article
- Genome-wide Association Study of Estradiol Levels and the Causal Effect of Estradiol on Bone Mineral Density.The Journal of clinical endocrinology and metabolism · 2021Article
- Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop.Communications biology · 2021Article
- Functional genomics based on germline genome-wide association studies of endocrine therapy for breast cancer.Pharmacogenomics · 2020Article
- Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial.Menopause (New York, N.Y.) · 2020Article
- Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives.Pharmacogenetics and genomics · 2020Article
- Single Nucleotide Polymorphisms at a Distance from Aryl Hydrocarbon Receptor (AHR) Binding Sites Influence AHR Ligand-Dependent Gene Expression.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome-Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2.Clinical pharmacology and therapeutics · 2019Article
- Single Nucleotide Polymorphisms (SNPs) Distant from Xenobiotic Response Elements Can Modulate Aryl Hydrocarbon Receptor Function: SNP-Dependent CYP1A1 Induction.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- TSPYL Family Regulates CYP17A1 and CYP3A4 Expression: Potential Mechanism Contributing to Abiraterone Response in Metastatic Castration-Resistant Prostate Cancer.Clinical pharmacology and therapeutics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 2 countries.
Funding
Abstract
We performed a discovery genome-wide association study to identify genetic factors associated with variation in plasma estradiol (E2) concentrations using DNA from 772 postmenopausal women with estrogen receptor (ER)-positive breast cancer prior to the initiation of aromatase inhibitor therapy. Association analyses showed that the single nucleotide polymorphisms (SNP) (rs1864729) with the lowest P value (P = 3.49E-08), mapped to chromosome 8 near TSPYL5. We also identified 17 imputed SNPs in or near TSPYL5 with P values < 5E-08, one of which, rs2583506, created a functional estrogen response element. We then used a panel of lymphoblastoid cell lines (LCLs) stably transfected with ERα with known genome-wide SNP genotypes to demonstrate that TSPYL5 expression increased after E2 exposure of cells heterozygous for variant TSPYL5 SNP genotypes, but not in those homozygous for wild-type alleles. TSPYL5 knockdown decreased, and overexpression increased aromatase (CYP19A1) expression in MCF-7 cells, LCLs, and adipocytes through the skin/adipose (I.4) promoter. Chromatin immunoprecipitation assay showed that TSPYL5 bound to the CYP19A1 I.4 promoter. A putative TSPYL5 binding motif was identified in 43 genes, and TSPYL5 appeared to function as a transcription factor for most of those genes. In summary, genome-wide significant SNPs in TSPYL5 were associated with elevated plasma E2 in postmenopausal breast cancer patients. SNP rs2583506 created a functional estrogen response element, and LCLs with variant SNP genotypes displayed increased E2-dependent TSPYL5 expression. TSPYL5 induced CYP19A1 expression and that of many other genes. These studies have revealed a novel mechanism for regulating aromatase expression and plasma E2 concentrations in postmenopausal women with ER(+) breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.