THE EFFECT OF FAMILY-SIZE ON ESTIMATES OF THE FREQUENCY OF HEREDITARYNONPOLYPOSIS COLORECTAL-CANCER

Diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is cur rently based on phenotypical analysis of an expanded pedigree. Diagnos tic guidelines ('Amsterdam criteria') proposed by the International Co llaborative Group on HNPCC are often too stringent for use with small families. There is also the possibility of false-positive diagnosis in large pedigrees that may contain chance clusters of tumours. This stu dy was conducted to determine the effect of family size on the probabi lity of diagnosing HNPCC according to the Amsterdam criteria. A total of 1052 patients with colorectal cancer were classified as HNPCC or no n-HNPCC according to the Amsterdam criteria. Associations between this diagnosis and the size of the first-degree pedigree were evaluated in logistic regression and linear discriminant analyses. Logistic regres sion showed a significant association for family size with the Amsterd am-criteria-based HNPCC diagnosis. Linear discriminant analysis showed that HNPCC diagnosis was most likely. to occur when first-degree pedi grees contained more than seven relatives. Failure to consider family size in phenotypic diagnosis of HNPCC can lead to both under- and over estimation of the frequency of this disease. Small pedigrees must be e xpanded to reliably exclude HNPCC. Positive diagnoses based on assessm ent of eight or more first-degree relatives should be supported by oth er clinical features.