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 #
7U01CA111257-09
Application #
8538881
Study Section
Special Emphasis Panel (ZCA1-SRLB-C (M1))
Program Officer
Mazurchuk, Richard V
Project Start
2004-09-27
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
9
Fiscal Year
2013
Total Cost
$541,643
Indirect Cost
$146,539
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
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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
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

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