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 supplemental dietary cellulose reduces the incidence of colon cancer. Epidemiology studies also indicate that high dietary fiber reduces the risk of colorectal cancer in humans. Patients diagnosed with sporadic adenomas were entered into a randomized clinical trial to determine if supplemental dietary cellulose would reduce the patients' risk for colon cancer. Immunohistochemical staining for transforming growth factor alpha (TGF-alpha) was done on biopsies of rectal mucosa taken from patients at the time of initial polypectomy and 1 year later. Results were evaluated 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 group 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 decrease the risk for colon cancer. Long-term testing of the ability of dietary cellulose to reduce adenoma recurrence is under way to validate the use of TGF-alpha as a surrogate end point biomarker.
Hardman
W E
WE
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762, USA.
Cameron
I L
IL
Beer
W H
WH
Speeg
K V
KV
Kadakia
S C
SC
Lang
K A
KA
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002482:Cellulose / Q000008:administration & dosage*; D003111:Colonic Polyps / Q000178:diet therapy / Q000473:pathology* / Q000517:prevention & control; D015179:Colorectal Neoplasms / Q000178:diet therapy / Q000473:pathology* / Q000517:prevention & control; D004043:Dietary Fiber / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000178:diet therapy / Q000473:pathology / Q000517:prevention & control; D011446:Prospective Studies; D051381:Rats; D012307:Risk Factors; D016211:Transforming Growth Factor alpha / Q000032:analysis*
D014408:Biomarkers, Tumor; D004043:Dietary Fiber; D016211:Transforming Growth Factor alpha; D002482:Cellulose