Complex segregation analysis was conducted in a series of patients with
hereditary non-polyposis
colorectal cancer (HNPCC) ascertained through probands registered in the
Cancer Registry of the
Health Care District of Modena, Northern Italy. Altogether there were 125
nuclear families
segregating for HNPCC, for a total of 672 individuals. The analysis favoured
a two-locus model, with
both susceptibility genes rare and dominant. The gene frequency of the
deleterious allele at the major
locus is estimated to be low qm=0·004 and for the second locus
the estimate is even lower q=0·00003. Both genes defining the
two-locus model seem to be highly penetrant. The lifetime
penetrance of the abnormal gene at the major locus is estimated to be
0·73 for female, while the
estimation for male is higher, 0·85.