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Metabolomic profiles as predictors of colorectal cancer risk

Principal Investigator
Name
Rashmi Sinha
Degrees
Ph.D.
Institution
NCI/DCEG
Position Title
Senior Investigator
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2010-0047
Initial CDAS Request Approval
Mar 1, 2010
Title
Metabolomic profiles as predictors of colorectal cancer risk
Summary
Metabolomics is a field of research devoted to the study of large numbers (400-800) of small molecules within biofluids, such as blood. Metabolomic profiles incorporate exposure from diet, lifestyle, the environment and genetics, among many other factors, that may be related to cancer risk. We propose performing a metabolome-wide association study (MWAS) using serum samples collected prospectively in a nested case-control study of colorectal cancer. Our three specific aims are to: 1) identify metabolites associated with colorectal cancer risk; 2) study the metabolic pathways linking known risk factors to colorectal cancer; 3) measure the risk of colorectal cancer attributable to nutritional and other difficult to measure exposures. Serum samples will be analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) and further analyzed by gas chromatography (GC)-TOFMS, as this technology permits measurements of additional metabolites not readily measured by UPLC-QTOFMS and can be linked to mass spectral reference libraries of known compounds. The findings from this project could provide a major advance in our understanding of potentially modifiable colorectal cancer risk factors and their underlying pathophysiology and mechanisms.
Aims

1. Identify metabolites related to an individual's risk of colorectal cancer. We will conduct a metabolome-wide association study (MWAS) to identify serum metabolites that predict colorectal cancer. Metabolic profiles have been shown to be predictors of several cancers, as well as cardiovascular disease, diabetes, and celiac disease and we hypothesize unique metabolites and metabolic profiles will similarly predict colorectal cancer. 2. Study the metabolic pathways linking known risk factors to colorectal cancer. By identifying those groups of metabolites that link exposures to cancer, we hope to gain a better understanding of mechanistic pathways of carcinogenesis. These groups of metabolic intermediates should provide insight into how the body responds to exposures and whether it is that response that mediates the risk of cancer. We hypothesize that groups of metabolites that correspond to exposures and pathways will be associated with colorectal cancer. 3. Measure the risk of colorectal cancer attributable to nutritional and other poorly measured exposures. Many nutritional and lifestyle exposures, such as physical activity, and consumption of fat, meat and energy, are poorly measured by questionnaires used in large epidemiological studies of cancer. Therefore, it has been equally difficult to quantify their true effects on cancer risk. Here, we intend to show that metabolic surrogates can serve as better estimates of nutritional and lifestyle exposures than the current methods, and then obtain accurate measures of the risk attributable to these exposures. In particular, we hypothesize that metabolomic profiles that characterize physical activity, obesity, and consumption of meat, fat, and energy will be associated with colorectal cancer.

Collaborators

Demetrius Albanes (NEB, DCEG, NCI)
Nilanjan Chatterjee (BB, DCEG, NCI)
Arthur Schatzkin (NEB, DCEG, NCI)
Andrew Patterson (CCR, NCI)
Rachael Stolzenberg-Solomon (NEB, DCEG, NCI)
Steven C. Moore (NEB, DCEG, NCI)
Samsiddhi Bhattacharjee (BB, DCEG, NCI)
Joshua Sampson (BB, DCEG, NCI)
Amanda Cross (NEB, DCEG, NCI)
Frank Gonzales (CCR, NCI)
Rashmi Sinha (DCEG/NCI)
Erikka Loftfeld (DCEG/NCI)

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