TRANSFORMING-GROWTH-FACTOR-ALPHA DISTRIBUTION IN RECTAL CRYPTS AS A BIOMARKER OF DECREASED COLON-CANCER RISK IN PATIENTS CONSUMING CELLULOSE

Data from rat experimental carcinogenesis studies indicate that supple mental dietary cellulose reduces the incidence of colon cancer. Epidem iology studies also indicate that high dietary fiber reduces the risk of colorectal cancer in humans. Patients diagnosed with sporadic adeno mas were entered into a randomized clinical trial to determine if supp lemental dietary cellulose would reduce the patients' risk for colon c ancer. Immunohistochemical staining for transforming growth factor alp ha (TGF-alpha) was done on biopsies of rectal mucosa taken from patien ts at the time of initial polypectomy and 1 year later. Results were e valuated for utility as a surrogate end point biomarker for reduction in colon cancer risk. There was a significant decrease in the fraction of the rectal crypt cells that stained for TGF-alpha in six of seven of the patients given the cellulose supplements but in only one of six of the patients not given cellulose. Thus, whether evaluated as a gro up or in individual patients, there was a significant decrease in TGF- alpha in rectal crypts due to cellulose intervention, which correlated with the expected ability of supplemental dietary cellulose to decrea se the risk for colon cancer. Long-term testing of the ability of diet ary cellulose to reduce adenoma recurrence is under way to validate th e use of TGF-alpha as a surrogate end point biomarker.