Summary of Study ST001091
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000730. The data can be accessed directly via it's Project DOI: 10.21228/M89X1C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001091 |
Study Title | Aspirin Metabolomics in Colorectal Cancer Chemoprevention (part 1 - Colon) |
Study Type | Untargeted high-resolution mass spectrometry profiling |
Study Summary | Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. The goal of this research is to elucidate the key metabolic changes that are responsible for the anticancer effects of aspirin in humans using untargeted metabolomics analysis. Metabolomics, or global metabolite profiling, is an emerging discipline that has the potential to transform the study of pharmaceutical agents. Our innovative approach will use high-resolution mass spectroscopy to detect thousands of metabolites in blood plasma and normal colon mucosa biopsies that were collected from participants in the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled trial of aspirin and/or folic acid supplementation for the prevention of colorectal adenomas. Participants in the trial were assigned with equal probability to three aspirin treatment arms (placebo, 81 mg, or 325 mg daily). Over the three-year treatment period, 81 mg/day of aspirin reduced the risk of adenomas, whereas the 325 mg/day dose had less effect. The aims of the current proposal are to identify metabolomic signatures, including specific metabolites and metabolic pathways, that are associated with aspirin treatment in blood and normal colon mucosal tissue of participants after three years of randomized aspirin treatment; and then to assess the associations of these metabolic signatures with adenoma risk and whether they mediate the reductions in risk due to 81 mg/day aspirin treatment. We will prioritize metabolites for study by evaluating metabolite levels in patients from the placebo and treatment arms while controlling the false discovery rate, use correlation analysis to enhance identification of relevant metabolic modules associated with these prioritized metabolites, and apply pathway mapping with post-hoc application of ion dissociation spectroscopy to representative metabolites to confirm pathway identification. Because aspirin is a multifunctional drug that is thought to modify numerous pathways with potential roles in carcinogenesis, a global discovery-based metabolomics approach is the best way to identify its key activities. The public health significance of this work is substantial because understanding the mechanism of aspirin’s anticancer effects is key to optimizing its use and to the development of novel drugs targeting the metabolic pathways identified. |
Institute | Emory University |
Department | School of Medicine |
Laboratory | Clincal Biomarkers Laboratory |
Last Name | Uppal |
First Name | Karan |
Address | 615 Michael Street, Atlanta, GA, 30322, USA |
kuppal2@emory.edu | |
Phone | (404) 727 5027 |
Submit Date | 2018-09-05 |
Num Groups | 3 |
Total Subjects | 325 |
Num Males | 214 |
Num Females | 111 |
Study Comments | Both pooled colon tissue samples and Clinical Biomarker Laboratory pooled plasma samples were used |
Analysis Type Detail | LC-MS |
Release Date | 2019-09-23 |
Release Version | 1 |
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Collection:
Collection ID: | CO001129 |
Collection Summary: | Fresh frozen normal colon mucosal tissue samples were collected from participants in the Aspirin/Folate Polyp Prevention Study [1, 2] at the year three (end of treatment) colonoscopy. After the endoscope was advanced to the cecum, biopsy specimens were obtained from the mid-ascending colon (5 cm above the ileocecal valve). Immediately after the biopsies were taken, they were removed from the forceps, placed into 1.8 ml freezer tubes and immersed in liquid nitrogen or a dry ice/ethanol slurry until storage in a -70C freezer. The specimens were shipped on dry ice from the clinical centers to the Dartmouth biorepository storage facility and subsequently to the metabolomics analysis lab at Emory University. In addition, a colon tissue reference was generated using normal colon tissue removed at surgery from an anonymous donor. References 1. Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. The New England journal of medicine. 2003;348(10):891-9. 2. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA : the journal of the American Medical Association. 2007;297(21):2351-9. |
Sample Type: | Colon mucosal tissue |
Storage Conditions: | Described in summary |