Loren Lipworth

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Vanderbilt University

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PLCO (Learn more about this study)

2014-0007

Mar 7, 2014

Metabolic profiling of serum in a prospective renal cell carcinoma study

Recent studies suggest that metabolic approaches may be essential in advancing research in cancer biology, with the goal of developing biomarkers that assess the metabolic etiology of a given tumor, identify metabolic changes that underlie biological effects, and assist in the identification and characterization of susceptibility. The proposed project will use mass spectrometry-based untargeted metabolic profiling of prospectively acquired pre-diagnostic serum biomarkers to identify putative RCC risk biomarkers and discern molecular pathways important in RCC etiology. This approach is particularly appealing for studying RCC, because metabolic disturbance is the signature effect for these malignancies, virtually all of the identified genes related to numerous inherited forms of RCC are involved in pathways that respond to metabolic stress, and known RCC risk factors, such as obesity and hypertension, profile metabolically in serum, so it is reasonable to examine metabolic profiles that might define case vs. control. The specific aims are: 1) To measure metabolic profiles in stored baseline serum collected among cohort participants who did and did not subsequently develop RCC by utilizing an untargeted metabolomics approach; 2) To identify metabolic signatures that may be uniquely associated with RCC risk in African Americans, and particularly with risk for papillary RCC. We will test our hypotheses in a pooled analysis within the participating prospective studies using a nested case-control approach and stored pre-diagnostic blood samples for a total of over 1,200 RCC cases and 2:1 matched controls: Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, Shanghai Men’s and Women’s Health Studies, Women’s Health Initiative, Southern Community Cohort Study, and Multiethnic Cohort. This will be the first and largest prospective study to generate mass spectrometry-based metabolomics data regarding sensitive and specific biomarkers for prediction of RCC risk in a multiethnic population.

The specific aims are:

Aim 1. To examine metabolites and metabolic profiles in stored serum collected among cohort participants who did and did not subsequently develop RCC by utilizing an untargeted metabolomics approach. The hypothesis is that biomarkers associated with RCC risk can be detected in the serum before overt presentation of the disease, and can elucidate phenotypic characteristics of RCC pathogenesis from a metabolic perspective.

Aim 2. To identify metabolites and metabolic signatures that may be uniquely associated with RCC risk in African Americans (AA), and particularly with risk for papillary RCC. The hypothesis is that putative biomarkers associated with RCC risk may differ in AA and European Americans (EA).

We will test these hypotheses for Aims 1 and 2 in a pooled analysis within the participating prospective studies using a nested case-control approach and pre-diagnostic blood for using a nested case-control approach and stored pre-diagnostic blood samples for a total of nearly 1,300 RCC cases and 2,600 matched controls.