Trial reportMolecular endocrinology (Baltimore, Md.)2014
Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics.
Trial report in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Pharmacogenetics of Toxicities Related to Endocrine Treatment in Breast Cancer: A Systematic Review and Meta-analysis.Cancer genomics & proteomicsPooled it
- Interaction Between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early-Stage Breast Cancer.Clinical pharmacology and therapeutics · 2021Trial
- Study of Estrogen Receptor-Mediated PGx-eQTLs Identifies Genetic Determinants of Breast Cancer Endocrine Therapy Response.International journal of molecular sciences · 2026Article
- SLMO2 inhibits apoptosis in ovarian cancer cells by modulating mitochondrial function via TRIAP1.Histology and histopathology · 2026Article
- No evidence for genotype-treatment interactions with breast cancer endocrine therapy adverse effects in UK Biobank.NPJ breast cancer · 2026Article
- Proteases and Osteoporosis: A Comprehensive Review of Their Role in Bone Health.Current drug targets · 2025Review
- Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy.Breast cancer research : BCR · 2024Article
- Cancer Treatment-Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy.Current treatment options in oncology · 2021Review
- Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management.Frontiers in endocrinology · 2021Review
- Review
- Aromatase Inhibitors-Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects.International journal of molecular sciences · 2020Review
- 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
- Cathepsin Z as a novel potential biomarker for osteoporosis.Scientific reports · 2019Article
- Osteoporosis and musculoskeletal complications related to therapy of breast cancer.Gland surgery · 2018Review
- Changes in bone mineral density in women with breast cancer receiving aromatase inhibitor therapy.Breast cancer research and treatment · 2018Observational
- Pathway-Based Analysis of Genome-Wide Association Data Identified SNPs inFrontiers in pharmacology · 2018Article
- SNPs near the cysteine proteinase cathepsin O gene (CTSO) determine tamoxifen sensitivity in ERα-positive breast cancer through regulation of BRCA1.PLoS genetics · 2017Article
- Article
- Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.Pharmacogenomics · 2017Review
- Estrogens and Androgens in Skeletal Physiology and Pathophysiology.Physiological reviews · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Bone fractures are a major consequence of osteoporosis. There is a direct relationship between serum estrogen concentrations and osteoporosis risk. Aromatase inhibitors (AIs) greatly decrease serum estrogen levels in postmenopausal women, and increased incidence of fractures is a side effect of AI therapy. We performed a discovery case-cohort genome-wide association study (GWAS) using samples from 1071 patients, 231 cases and 840 controls, enrolled in the MA.27 breast cancer AI trial to identify genetic factors involved in AI-related fractures, followed by functional genomic validation. Association analyses identified 20 GWAS single nucleotide polymorphism (SNP) signals with P < 5E-06. After removal of signals in gene deserts and those composed entirely of imputed SNPs, we applied a functional validation "decision cascade" that resulted in validation of the CTSZ-SLMO2-ATP5E, TRAM2-TMEM14A, and MAP4K4 genes. These genes all displayed estradiol (E2)-dependent induction in human fetal osteoblasts transfected with estrogen receptor-α, and their knockdown altered the expression of known osteoporosis-related genes. These same genes also displayed SNP-dependent variation in E2 induction that paralleled the SNP-dependent induction of known osteoporosis genes, such as osteoprotegerin. In summary, our case-cohort GWAS identified SNPs in or near CTSZ-SLMO2-ATP5E, TRAM2-TMEM14A, and MAP4K4 that were associated with risk for bone fracture in estrogen receptor-positive breast cancer patients treated with AIs. These genes displayed E2-dependent induction, their knockdown altered the expression of genes related to osteoporosis, and they displayed SNP genotype-dependent variation in E2 induction. These observations may lead to the identification of novel mechanisms associated with fracture risk in postmenopausal women treated with AIs.
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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.