A bile acid-induced apoptosis assay for colon cancer risk and associated quality control studies

Bile acids are important in the etiology of colorectal cancer. Bile acids i nduce apoptosis in colonic goblet cells at concentrations comparable to tho se found in fecal water after high-fat meals, Preliminary evidence indicate d that cells of the normal-appearing (nontumorous) portion of the colon epi thelium of colon cancer patients are more resistant to bile salt-induced ap optosis than are cells from normal individuals. In the present study, 68 patients were examined, and biopsies were taken at 20 cm from the anal verge, cecum, and descending colon. The patients inclu ded 17 individuals with a history of colorectal cancer, 37 individuals with adenomas, and 14 individuals who were neoplasia free. The mean bile salt-i nduced apoptotic index among normal individuals was 57.6 +/- 3.47 (SE), whi ch differed significantly (P < 0.05) from the mean value of 36.41 +/- 3.12 in individuals with a history of colon cancer. The correlation between independent observers was 0.89 (P < 0.001), indicat ing good interobserver reliability, Components of variance comparing interi ndividual versus intraindividual sources of variation suggested that site-t o-site variability, both between regions of the colon and for adjacent biop sies, was larger than the interpatient variability for individuals with a h istory of neoplasia, Therefore, there was "patchiness" of the susceptibilit y of regions of the colon to bile acid-induced apoptosis in individuals wit h a history of neoplasia (a patchy field effect). There was no obvious corr elation of low-apoptotic index regions with regions in which previous neopl asias had been found and removed. On the other hand, for normal, i.e., neop lasia-free, individuals, there was relatively less intraindividual variatio n compared to interindividual variation. Our assay shows an association between resistance to bile acid-induced apop tosis, measured at 20 cm from the anal verge, and colon cancer risk. Thus, this assay may prove useful as a biomarker of colon cancer risk.