Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from ( super(3)H)thymidine labeling patterns in colonic epithelial cells

A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. From biopsies of colonic mucosa which are labeled with ( super(3)H)thymidine in vitro the degree of similarity of each subject's cell-labelling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. A linear score was calculated for each individual relative to each reference population and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk.