Colorectal cancer is one of the most common malignancies in the United States and many other countries. Most colorectal cancers arise from adenomatous polyps, pre-malignant lesions that can be removed during an endoscopic procedure to reduce cancer incidence and mortality. Despite considerable research conducted over the past few decades, very few biomarkers have proven useful in assessing individual risk for developing colorectal neoplasia. As part of the renewal for the Tennessee Colorectal Polyp Study (TCPS), we propose to evaluate whether high endogenous production and signaling of prostaglandin E2, a key mediator of COX-2 pathway, may be related to the risk of colorectal adenomas and whether PGE2 -related association may be independent of a low-grade, systematic inflammation, as measured by blood C- reactive protein (CRP). Urinary PGE2 metabolite and blood CRP will be measured in approximately 1000 adenoma patients and polyp-free controls to evaluate the utility of these biomarkers in risk assessment. A two-phase study involving approximately 4600 subjects will be conducted to evaluate polymorphisms in genes affecting PGE2 production (PTGS2, PTGES, 15-PGDH) and signaling (PTGER1-PTGER4) in relation to adenoma risk. Expression levels of genes related to PGE2 production in polyp tissues will be quantified using RT-PCR and correlated with the level of urinary PGE2 metabolite. In addition, we will also investigate risk factors for sessile serrated adenomas (SSA), a group of newly-defined adenomas that may have a different risk profile compared to conventional adenomas. The TCPS is a large, on-going colonoscopy-based epidemiologic study of colorectal adenomas. The resources established in this study will provide exceptional opportunities to test the hypotheses proposed in this application. Results from this study will be valuable for identifying high-risk individuals for cost-effective colorectal screening and chemoprevention.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA095103-09
Application #
8073537
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
9
Fiscal Year
2010
Total Cost
$401,486
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Davenport, James R; Su, Timothy; Zhao, Zhiguo et al. (2018) Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps. Gut 67:456-465
Liu, Qi; Herring, Charles A; Sheng, Quanhu et al. (2018) Quantitative assessment of cell population diversity in single-cell landscapes. PLoS Biol 16:e2006687
Means, Anna L; Freeman, Tanner J; Zhu, Jing et al. (2018) Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer. Cell Mol Gastroenterol Hepatol 6:257-276
Weiss, Vivian L; Kiernan, Colleen; Wright, Jesse et al. (2018) Fine-Needle Aspiration-Based Grading of Pancreatic Neuroendocrine Neoplasms Using Ki-67: Is Accurate WHO Grading Possible on Cytologic Material? J Am Soc Cytopathol 7:154-459
Roberts, Jordan; Gonzalez, Raul S; Revetta, Frank et al. (2018) Mesenteric tumour deposits arising from small-intestine neuroendocrine tumours are frequently associated with fibrosis and IgG4-expressing plasma cells. Histopathology 73:795-800
Gibson, William E; Gonzalez, Raul S; Cates, Justin M M et al. (2018) Hepatic micrometastases are associated with poor prognosis in patients with liver metastases from neuroendocrine tumors of the digestive tract. Hum Pathol 79:109-115
Fenix, Aidan M; Neininger, Abigail C; Taneja, Nilay et al. (2018) Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes. Elife 7:
Wang, Jing; Zhao, Yue; Zhou, Xiaofan et al. (2018) Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation. BMC Genomics 19:633
Burns, Michael C; Howes, Jennifer E; Sun, Qi et al. (2018) High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling. Anal Biochem 548:44-52
Herring, Charles A; Banerjee, Amrita; McKinley, Eliot T et al. (2018) Unsupervised Trajectory Analysis of Single-Cell RNA-Seq and Imaging Data Reveals Alternative Tuft Cell Origins in the Gut. Cell Syst 6:37-51.e9

Showing the most recent 10 out of 447 publications