Familial heterogeneity of colon cancer risk.

Abstract

The authors have assembled detailed family histories of cancer on 857 cancer probands, of whom 180 manifested colorectal carcinoma. This study determines if some families had a greater risk for colorectal cancer than others, and if so, what factors were associated with an increase in risk. To test for the possibility of heterogeneity of risk, a parameter called the Z-score, was calculated for each family. The Z-score is a measure of the number of cancer cases in the family adjusted for the number of expected cases. A permutation test was employed to test whether or not the variance of Z-scores from the sample was greater then expected by random chance. The variance for families ascertained through colon cancer probands, but not in any of the other groups, was significantly increased. Of the colon group, 10.6% fell into a high-risk category, as did 5.56% of the rectal cancer families, but only 3.95% of the other groups combined were at high risk. Anatomic sites (in the proband) with the highest Z-score variances were sigmoid and transverse colon, whereas lower variances were seen for cecum and descending colon. Risk status therefore may be partially dependent upon exact anatomic sites within the colon. The effect of proband's age of diagnosis was not significant, but did show the possibility of an effect on heterogeneity of risk for both the younger and older groups.