While colonoscopy is proven to decrease colorectal cancer (CRC) fatalities, its expense, complications and limited availability makes it impractical for general population screening. Risk-stratification through assessment of the """"""""field effect"""""""" of colon carcinogenesis can be used to determine the need for colonoscopy; however current markers (e.g. distal colonic adenomatous polyp) are clearly inadequate. Dr. Backman's group and colleagues, having pioneered light-scattering technologies for detecting dysplastic cells (Nature 2000 & Nature Med 2001), now have developed four-dimensional light-scattering fingerprinting (4D-ELF), which enables quantitative analysis of nano-scale cellular architecture. Using 4D-ELF, we discovered spectral markers in histologically normal mucosa that preceded all conventional biomarkers of experimental CRC (Gastroenterology 2004). Evaluating 4D-ELF signatures from the uninvolved rectal mucosa had unprecedented sensitivity and positive predictive value (>98%) for the future occurrence of neoplasia. Pilot human studies confirmed the promise of these novel biomarkers. We propose to further validate these spectral markers by using an endoscopically-compatible 4D-ELF probe during colonoscopy. Based on rectal 4D-ELF analysis from 500 patients, we will formulate prediction rules for both the occurrence of advanced polyps/cancers and the exclusion of neoplasia (thus identifying a subgroup not requiring further screening). We will prospectively test these rules in 750 patients. Furthermore, we will use hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis as a paradigm to investigate whether the unparalleled sensitivity of 4D-ELF may detect long-term CRC risks engendered by an inherited predisposition. We will evaluate the ability of spectral marker to both identify mutations and forecast phenotypic presentation. In the future these spectral markers may be assayed with a 4D-ELF probe during rectal examination, thus providing a practical and accurate means of determining the optimal CRC screening regimen.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA111257-01
Application #
6848173
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O1))
Program Officer
Wagner, Paul D
Project Start
2004-09-27
Project End
2009-08-31
Budget Start
2004-09-27
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$367,747
Indirect Cost
Name
Northshore University Healthsystem Research Institute
Department
Type
DUNS #
154538107
City
Evanston
State
IL
Country
United States
Zip Code
60201
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Wali, Ramesh K; Hensing, Thomas A; Ray, Daniel W et al. (2014) Buccal microRNA dysregulation in lung field carcinogenesis: gender-specific implications. Int J Oncol 45:1209-15
Stypula-Cyrus, Yolanda; Mutyal, Nikhil N; Dela Cruz, Mart et al. (2014) End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis. FEBS Lett 588:829-35
Patel, Mihir; Gomes, Andrew; Ruderman, Sarah et al. (2014) Polarization gating spectroscopy of normal-appearing duodenal mucosa to detect pancreatic cancer. Gastrointest Endosc 80:786-93.e1-2

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