In order to realize the promise of precision medicine, more and better biomarkers are needed to guide clinical decision making. This is of particular importance for patients with colorectal cancer (CRC) as: 1. CRC is the third most common cancer in both men and women accounting for 9% of all incident cancers in the United States; 2. The 5-year survival rates for the most common cancers in men and women, prostate and breast cancer, are 99% and 89%, respectively, but is only 64% for CRC making it the second most common cause of cancer related death in the U.S.; 3. At present there is a lack of clinically useful biomarkers predictive of recurrence or survival for CRC patients that can be used to guide surveillance and treatment. Consequently, there are issues of both overtreatment and undertreatment because treatment is based largely on clinical and pathologic parameters, but little else to risk stratify patients. This study will utilize 1,574 participants in a multi- cente prospective cohort (the ColoCare Study) of newly diagnosed CRC patients. Detailed demographic, clinical, epidemiologic, and follow-up data are ascertained on all participants along with blood samples collected at multiple time points. Thus, this study is specifically designed to meet the overarching goal of this proposal, the discovery and verification of novel blood-based biomarkers predictive of recurrence among CRC patients, through achieving the following specific aims: 1. Discovery and verification of novel biomarkers predictive of recurrence among CRC patients: Utilizing samples collected at the time of diagnosis we will evaluate the plasma proteome, glycome, and autoantibody repertoire, including assessment of promising markers reported in the literature, using well-validated laboratory approaches to identify markers predictive of risk of recurrence for well-defined clinical applications (predictin recurrence in stage I/II patients and in stage III patients). Top candidates from our discovery experiments meeting particular statistical criteria will be evaluated in a group of patients completely separate from those used in the discovery set. 2. Discovery and verification of novel biomarkers useful for the early detection of CRC recurrence: Utilizing serial samples collected at regular intervals post-diagnosis we will discover novel biomarkers potentially useful for disease monitoring using proteomic, glycomic, and autoantibody platforms. Markers will be evaluated in the context of CEA, a clinically used biomarker of recurrence that has a 60% sensitivity and 90% specificity for detecting recurrent colorectal cancer in stage II and III patients. If successfl this project could lead to the development of clinical grade biomarker assays that could have significant impact on reducing the morbidity and mortality associated with colorectal cancer. This study is innovative in that the cohort that will be used is unique, highly characterized, and possesses serial samples collected at regular intervals; the unique platforms that will be used have been shown to yield potentially useful biomarkers and can also evaluate existing markers of interest; and this study is powered to identify biomarkers with clinically meaningful performance characteristics.

Public Health Relevance

Colorectal cancer is the second most common cancer related cause of mortality in the United States, yet there are limited approaches to predict risk of poor outcomes among those diagnosed with this cancer. The overarching goal of this proposal is to discover and verify novel blood-based biomarkers predictive of recurrence among colorectal cancer patients. This study utilizes a well-defined prospective cohort of newly diagnosed colorectal cancer patients and is designed to identify biomarkers that could have meaningful clinical impact.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA189184-04
Application #
9478138
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Elena, Joanne W
Project Start
2015-05-01
Project End
2020-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Gigic, Biljana; Boeing, Heiner; Toth, Reka et al. (2018) Associations Between Dietary Patterns and Longitudinal Quality of Life Changes in Colorectal Cancer Patients: The ColoCare Study. Nutr Cancer 70:51-60
Neumeyer, Sonja; Banbury, Barbara L; Arndt, Volker et al. (2018) Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer. Br J Cancer 118:1639-1647
Sheth, Harsh; Northwood, Emma; Ulrich, Cornelia M et al. (2018) Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations. PLoS One 13:e0192223
Barault, Ludovic; Amatu, Alessio; Siravegna, Giulia et al. (2018) Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer. Gut 67:1995-2005
Delphan, Mahmoud; Lin, Tengda; Liesenfeld, David B et al. (2018) Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: Results from the ColoCare Study. Metabolomics 2018:
Himbert, Caroline; Ose, Jennifer; Nattenm├╝ller, Johanna et al. (2018) Body fatness, adipose tissue compartments and biomarkers of inflammation and angiogenesis in colorectal cancer: the ColoCare Study. Cancer Epidemiol Biomarkers Prev :
Barrow, Timothy M; Klett, Hagen; Toth, Reka et al. (2017) Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study. J Pathol 243:366-375
Himbert, Caroline; Thompson, Henry; Ulrich, Cornelia M (2017) Effects of Intentional Weight Loss on Markers of Oxidative Stress, DNA Repair and Telomere Length - a Systematic Review. Obes Facts 10:648-665
Himbert, Caroline; Delphan, Mahmoud; Scherer, Dominique et al. (2017) Signals from the Adipose Microenvironment and the Obesity-Cancer Link-A Systematic Review. Cancer Prev Res (Phila) 10:494-506

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