Abstract
New analytical methods have been developed for measurement of the height distribution patterns of [3H]dThd-labeled epithelial cells in colonic crypts of high- and low-risk population groups. Labeled cells were segregated with respect to crypt-height into 10 compartments of equal size, plus a lumenal surface compartment for each subject. Members of families prone to polyposis coli and to non-polyposis colon cancer were compared to subjects at lower risk. The latter included persons from polyp-free and cancer-free branches of the same families, normal controls, and patients with colon cancer from the general population. Significant differences were found between groups of patients with familial polyposis or familial colon cancer and subjects at low risk, when labeled cell distributions were compared over all the crypt height compartments (p <0.001). Distributions of the occupancy fractions of labeled cells in the upper region (i.e. 40%) of the crypt (Φh), measured for the fraction of each population (Φp), revealed a discriminant level that separated over 90% of low-risk subjects from a major fraction of those affected with familial colon cancer or polyposis and from close to one-half of the at-risk progeny as expected for an autosomal dominant trait. However, subjects with colon cancer in the general population had (Φp,Φh) distributions closer to the low-risk groups, although a subgroup of patients had abnormal (Φh), values characteristic of hereditary disease. Thus, the (Φp,Φh) distribution appears to be a more precise measure of risk than previously used in discriminating populations with genetic susceptibility to colon cancer from those at lower risk and may be useful as a marker to identify individuals with the at-risk phenotype.