Date of Completion

4-24-2018

Embargo Period

10-21-2018

Keywords

aberrant crypt foci, proximal colon, screening colonoscopy, tumor microenvironment, microgenomics, alternative pathway, interval cancer, sessile serated adenomas

Major Advisor

Daniel W. Rosenberg

Associate Advisor

Blanka Rogina

Associate Advisor

Carol C. Pilbeam

Associate Advisor

James J. Grady

Associate Advisor

Charles Giardina

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer related death in the United States. CRC is believed to develop through a multistage adenoma-carcinoma sequence, where polyps represent an intermediate, precursor lesion to advanced cancer. Recent success in CRC prevention has been largely attributed to the interruption of this process through the widespread implementation of endoscopic polypectomy. Although the overall rates of CRC have declined, there has been an observable shift in the distribution of CRCs to the proximal colon, in particular among patients who develop 'interval' CRC, cancers that arise between negative screening colonoscopies. Novel strategies and biomarkers are needed to further reduce overall rates of CRC and identify individuals at increased risk for proximal adenomas and CRC. By studying polyps and aberrant crypt foci (ACF), the earliest detectable lesion in the human colon, we will be able to gain a better understanding of the mechanisms and epidemiological risk factors of early proximal colon carcinogenesis.

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