Lay Summary

Proposal No.   IBD-0099R
Principal Investigator:  Christoph Hanski, Ph.D.
Applicant Organization:   Charité Universitätsmedizin Berlin, Campus Benjamin Franklin (Germany)
Project Title:  Effects of deoxycholic acid and ursodeoxycholic acid on the development of carcinomas during chronic ulcerative colitis:  proof of principle in an animal model
Period of Award:  March 1, 2004 – June 30, 2006

Chronic ulcerative colitis, depending on its extent and duration, increases 10-20 times the risk of developing colon cancer.  Patients with diagnosed precancerous lesions usually undergo removal of the colon (colectomy) to prevent the development of the cancer.  Preventive measures that would inhibit or slow down the development of cancer are needed to avoid colectomy.

Patients with ulcerative colitis and primary sclerosing cholangitis (PSC), a condition associated with the obstruction of the bile ducts leading to the reduction of bile flow, are known to have a three-five fold higher risk of developing colon cancer than the ulcerative colitis patients without PSC.  The treatment of PSC with ursodeoxycholic acid (UDCA) was recently shown to reduce the risk of colon cancer in these patients.  Whether UDCA would also reduce the colon cancer risk of patients without PSC is not known and the analysis of this question in a clinical setting requires a long-term study.

In the present proposal, this question should be answered by using mice with ulcerative colitis that develop colon cancer within several months.  If colon cancer prevention by treatment with UDCA can be demonstrated in this model, the mechanism of the preventive action can be investigated in detail and a prospective study with UC patients can be envisaged.