Colorectal cancer (CRC) remains the second leading cause of cancer deaths among Americans largely due to inability to screen the ~100 million Americans >/=50 years old with colonoscopy because of the expense, discomfort, potential complications and lack of adequate endoscopic capacity. This is juxtaposed with the inefficiency of screening colonoscopies in that only ~5-6% yield "screening relevant neoplasia" (advanced adenomas or early CRC). Even in patients with a personal history of adenomas and thus deemed to be at higher risk, the yield of surveillance colonoscopy is still <10%. Thus, there is an urgent need for a minimally intrusive risk stratification technique. Our biomarker development laboratory has focused on developing innovative light-scattering technologies to identify the micro-architectural correlates of the genetic/epigenetic changes in field carcinogenesis. We have used early techniques to prove that interrogation of the microscopically-normal rectal mucosa can predict concurrent neoplasia throughout the colon. In this competitive renewal, we plan to develop a novel technique, partial wave spectroscopy (PWS) that enables unprecedented quantitative characterization of the nanoscale architecture through analysis of brushed or extruded cells. Our preliminary data suggests that PWS signatures paralleled neoplastic progression in experimental models. In humans, rectal brushings were able to accurately predict concurrent neoplasia. These nanoscale alterations appear robust in that they represent a final common manifestation for heterogeneous genetic/epigenetic alterations. We propose to develop novel PWS signatures for prediction rule optimization and then use a training/testing set design to assess the ability to rectal PWS analysis to predict concurrent neoplasia in 1000 patients. We will assess another 500 patients to predict recurrence of personal history of adenomas (surveillance). Finally, we will explore novel approaches such as PWS analysis of fecal-derived colonocytes and compare the rectal PWS with molecular marker Muc 4 (developed in our BDL) and cellular markers (proliferation versus apoptosis). This should provide a highly accurate, minimally intrusive technique to allow risk-stratification and hence tailoring of CRC screening regimen.

Public Health Relevance

Colorectal cancer is eminently potential through identification and removal of adenomatous polyps by colonoscopy. However, despite performing ~18-20 million colonoscopies per year, CRC kills 50,000 Americans per year. Because >90% of colonoscopies are negative for significant lesions, our goal is to develop a minimally-intrusive approach allow colonoscopy to cover more of the population but only patients likely to derive benefit from the test.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
6U01CA111257-08
Application #
8310116
Study Section
Special Emphasis Panel (ZCA1-SRLB-C (M1))
Program Officer
Mazurchuk, Richard V
Project Start
2004-09-27
Project End
2013-01-31
Budget Start
2012-07-01
Budget End
2013-01-31
Support Year
8
Fiscal Year
2012
Total Cost
$602,303
Indirect Cost
$132,491
Name
Northshore University Healthsystem
Department
Type
DUNS #
069490621
City
Evanston
State
IL
Country
United States
Zip Code
60201
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
Cruz, Mart Dela; Wali, Ramesh K; Bianchi, Laura K et al. (2014) Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender. Cancer Epidemiol Biomarkers Prev 23:2413-21
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
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
Mutyal, Nikhil N; Radosevich, Andrew; Tiwari, Ashish K et al. (2013) Biological mechanisms underlying structural changes induced by colorectal field carcinogenesis measured with low-coherence enhanced backscattering (LEBS) spectroscopy. PLoS One 8:e57206
Roy, Hemant K; Damania, Dhwanil P; DelaCruz, Mart et al. (2013) Nano-architectural alterations in mucus layer fecal colonocytes in field carcinogenesis: potential for screening. Cancer Prev Res (Phila) 6:1111-9
Calderwood, Audrey H; Roy, Hemant K (2013) Increasing colorectal cancer screening adherence: comment on "A randomized comparison of print and web communication on colorectal cancer screening". JAMA Intern Med 173:129-31
Damania, Dhwanil; Roy, Hemant K; Subramanian, Hariharan et al. (2012) Nanocytology of rectal colonocytes to assess risk of colon cancer based on field cancerization. Cancer Res 72:2720-7
Backman, Vadim; Roy, Hemant K (2011) Light-scattering technologies for field carcinogenesis detection: a modality for endoscopic prescreening. Gastroenterology 140:35-41
Tiwari, Ashish K; Crawford, Susan E; Radosevich, Andrew et al. (2011) Neo-angiogenesis and the premalignant micro-circulatory augmentation of early colon carcinogenesis. Cancer Lett 306:205-13

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