Trial reportCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2016
Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial.
Trial report in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses 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
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Aspirin use for cancer prevention: A systematic review of public, patient and healthcare provider attitudes and adherence behaviours.Preventive medicine · 2022Pooled it
- Pooled it
- Plasma Metabolomics Analysis of Aspirin Treatment and Risk of Colorectal Adenomas.Cancer prevention research (Philadelphia, Pa.) · 2022Trial
- A Randomized Double-blind Placebo-controlled Trial of Oral Aspirin for Protection of Melanocytic Nevi Against UV-induced DNA Damage.Cancer prevention research (Philadelphia, Pa.) · 2022Trial
- Metabolomics Analysis of Aspirin's Effects in Human Colon Tissue and Associations with Adenoma Risk.Cancer prevention research (Philadelphia, Pa.) · 2020Trial
- Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women.PloS one · 2017Trial
- Fatty acid metabolism and colon cancer protection by dietary methyl donor restriction.Metabolomics : Official journal of the Metabolomic Society · 2021Article
- Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- ASA Suppresses PGEPharmaceuticals (Basel, Switzerland) · 2020Article
- Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Investigations in the possibility of early detection of colorectal cancer by gas chromatography/triple-quadrupole mass spectrometry.Oncotarget · 2017Article
- Targeting the Metabolic Reprogramming That Controls Epithelial-to-Mesenchymal Transition in Aggressive Tumors.Frontiers in oncology · 2017Review
- Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer.Scientific reports · 2016Article
- Aspirin and colorectal cancer: the promise of precision chemoprevention.Nature reviews. Cancer · 2016Review
- Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics and lipidomics.Metabolomics : Official journal of the Metabolomic SocietyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundAspirin use is an effective strategy for the chemoprevention of colorectal cancer, even at low doses. However, in order to implement aspirin interventions, risk-benefit balances and biologic mechanisms need to be better defined; to further this aim, we used a metabolomics approach.
methodsWe metabolically profiled 40 healthy, nonsmoking men and women ages 20 to 45 years enrolled in a randomized, double-blind, crossover trial of 325 mg aspirin/day over a period of 60 days. Gas and liquid chromatography-mass spectrometry were used to comprehensively profile participants' plasma samples after aspirin and placebo interventions.
resultsA total of 363 metabolites, covering most human biochemical pathways, were measured. Compared with placebo-treated participants, plasma concentrations of the oncometabolite 2-hydroxyglutarate (R+S) decreased after aspirin treatment in both men and women (P = 0.005). This signal proved robust during 20-fold random splitting of the data using 80% of the samples in each split. We subsequently performed functional follow-up studies using targeted, enantiospecific detection in human colorectal cancer cell lines and observed an aspirin-induced reduction of (R)-2-hydroxyglutarate. We further showed that salicylate, the primary aspirin metabolite, inhibits the hydroxyacid-oxoacid transhydrogenase mediated production of (R)-2-hydroxyglutarate, thereby providing mechanistic evidence for the clinically observed effects of aspirin on total-2-hydroxyglutarate.
conclusionsUsing a metabolomics approach with functional follow-up, we propose that a decrease in the oncometabolite (R)-2-hydroxyglutarate may identify an additional mechanism for aspirin or its metabolites in cancer prevention. IMPACT: Reduction of the oncometabolite (R)-2-hydroxyglutarate identifies a novel, non-COX-inhibition-mediated mechanism of aspirin.
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.