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 lifeHong 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 forsptimum accuracy;Nearly half of a million people have UC iWIhe 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 nebplasia. 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 earcinogenesis in UC, and to use this

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA068124-15
Application #
7741235
Study Section
Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
Program Officer
Wagner, Paul D
Project Start
1995-07-25
Project End
2011-12-31
Budget Start
2010-04-23
Budget End
2011-12-31
Support Year
15
Fiscal Year
2010
Total Cost
$353,987
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Salk, Jesse J; Bansal, Aasthaa; Lai, Lisa A et al. (2013) Clonal expansions and short telomeres are associated with neoplasia in early-onset, but not late-onset, ulcerative colitis. Inflamm Bowel Dis 19:2593-602
Ussakli, Cigdem Himmetoglu; Ebaee, Anoosheh; Binkley, Jennifer et al. (2013) Mitochondria and tumor progression in ulcerative colitis. J Natl Cancer Inst 105:1239-48
Zisman, Timothy L; Bronner, Mary P; Rulyak, Stephen et al. (2012) Prospective study of the progression of low-grade dysplasia in ulcerative colitis using current cancer surveillance guidelines. Inflamm Bowel Dis :
Lai, Lisa A; Risques, Rosa Ana; Bronner, Mary P et al. (2012) Pan-colonic field defects are detected by CGH in the colons of UC patients with dysplasia/cancer. Cancer Lett 320:180-8
Risques, Rosa Ana; Lai, Lisa A; Himmetoglu, Cigdem et al. (2011) Ulcerative colitis-associated colorectal cancer arises in a field of short telomeres, senescence, and inflammation. Cancer Res 71:1669-79
May, Damon; Pan, Sheng; Crispin, David A et al. (2011) Investigating neoplastic progression of ulcerative colitis with label-free comparative proteomics. J Proteome Res 10:200-9
Bronner, Mary P; Skacel, Marek; Crispin, David A et al. (2010) Array-based comparative genomic hybridization in ulcerative colitis neoplasia: single non-dysplastic biopsies distinguish progressors from non-progressors. Mod Pathol 23:1624-33
Salk, Jesse J; Salipante, Stephen J; Risques, Rosa Ana et al. (2009) Clonal expansions in ulcerative colitis identify patients with neoplasia. Proc Natl Acad Sci U S A 106:20871-6
Brentnall, Teresa A; Pan, Sheng; Bronner, Mary P et al. (2009) Proteins That Underlie Neoplastic Progression of Ulcerative Colitis. Proteomics Clin Appl 3:1326
Risques, Rosa Ana; Lai, Lisa A; Brentnall, Teresa A et al. (2008) Ulcerative colitis is a disease of accelerated colon aging: evidence from telomere attrition and DNA damage. Gastroenterology 135:410-8

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