Rachael Solomon

Ph.D., M.P.H., R.D.

DCEG/NCI

Senior Investigator

PLCO (Learn more about this study)

2016-0003

Jun 2, 2016

Repeated measures of metabolomic profiles and pancreatic cancer in PLCO

Pancreatic cancer is the fourth leading cause for cancer mortality in the United States. As there are no effective screening methods for detection of this malignancy, it is typically diagnosed at advanced stages, which contributes to a five-year survival rate of 6.7 (worst of all cancers). The present proposed study builds upon the approved EEMS 2012-00066 by utilizing one additional serial blood sample closest to the time the case was diagnosed to determine metabolites that will be useful for detection of early disease, as well as understanding the biology of pancreatic cancer. We propose to measure metabolites in a subset of participants that are part of the baseline T0 set and have serial serum samples. Incorporating the serial PLCO samples within our baseline nested case-control set at this same time will allow us to handle and measure metabolites in the baseline and serial serum sample consecutively. We have observed that differential handling of samples (i.e. thawing and aliquoting in different laboratories) influences the concentrations of measured metabolites. We plan to carefully thaw the never thawed serum parent vials, aliquot, and snap freeze aliquots in a controlled, standard manner with minimal thaw time. As the pancreas is a major organ involved in metabolic regulation, we hypothesize the metabolomics approach will likely uncover biochemical pathways unique to pancreatic carcinogenesis including tumor proliferation and systemic response to the tumor. In this regard, the repeated measure of metabolites will help distinguish metabolites related to tumor biology from metabolic exposures associated with risk.

We have approval (EEMS 2012-00066) for a nested case-control study that uses baseline T0 samples with the aim to replicate the results observed in the ATBC cohort in an independent nested case-control study and pool results. The present study builds upon the approved study by utilizing serial blood collections. In total, the proposed study will include one serial serum sample closest to the time the case was diagnosed from 262 cases and controls with T0 baseline serum measured in EEMS 2012-00066.

Primary aim:
1) To determine whether changes in metabolite concentrations over time are associated with future diagnosis of PDA. We hypothesize that changes in unique metabolites and metabolomics profiles will be associated with PDA.

Secondary aim:
1) To determine whether metabolite concentrations are associated with early-stage and late stage PDA. Here, we will examine associations stratified by time since blood draw. We will conduct an association study, using a non-targeted approach to identify serum metabolites associated with early stage PDA among blood samples collected more than 5 years prior to cancer diagnosis and late stage disease among blood samples collected within 5 years of cancer diagnosis. We hypothesize that unique metabolites and metabolomics profiles will be correspond with different stages of PDA.