Biomarkers of UC Tumorigenesis

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DESCRIPTION (provided by applicant): Patients with extensive ulcerative colitis (UC) of more than 8 years duration have an increased risk of colorectal cancer which approximates 1% per year of colitis. Thus, a patient who has 20 years of UC will have a neoplastic risk that approximates 20%. The current standard of practice in all patients with longstanding UC is to perform life-long colonoscopic surveillance for colorectal cancer. There are major problems regarding surveillance including: 1) the large surface area of the colon; 2): dysplasia may arise anywhere within this large area and frequently produces no endoscopically visible lesion; 3) the diagnosis of dysplasia in inflammatory, bowel disease is a subjective interpretation and requires an experienced pathologist for optimum accuracy; Nearly half of a million people have UC in the United States; cancer surveillance in these patients is costly, time intensive, recurrent (every 1-2 years), and life-long. The long term objectives of this research are to better understand the molecular mechanisms of neoplastic progression in (UC) and to use this knowledge for improved surveillance of curable cancer and its precursors. Our previous studies have made it clear that even the non-dysplastic mucosa is genetically abnormal in UC patients who have neoplasia. In fact, the entire colon appears to show genetic instability in UC patients with cancer or dysplasia. We believe that this information is central to understanding the underlying causes of neoplastic progression and for developing new methods for cancer surveillance of UC patients. Such new methods could change the face of clinical care for these patients and their providers. Our goals remain to better understand the genomic changes during carcinogenesis in UC, and to use this knowledge to find early markers that will enable us to concentrate our surveillance efforts on those patients most likely to benefit from them. Both of these goals will help provide the underpinnings for development of cancer prevention strategies in the future.