Hereditary Colorectal Cancer: A Commentary

Abstract

The human geneticists, unfortunately perhaps and against the advice of the relevant clinicians, have opted for APC as the name for the familial adenomatous polyposis gene because a genetic disease is necessarily familial. However, perhaps FAP can remain the name for the syndrome itself. The uniformity of its distribution worldwide supports its maintenance by mutation-selection balance. Using the frequency of sporadic cases, estimated from complete registers through the frequency of cases with unaffected parents, the mutation rate estimate for the APC gene is from 1:100,000 to 1:125,000 depending on an assumed incidence of 1:10,000 or 1:5,000 and a frequency of sporadic cases of either 40% or 20%. The high mutation rate implies that most families will be new mutants and perhaps suggests the possibility of a large gene. Local drift may give rise to clusters of families in a given area with the same mutation, and this may be the case, for example, for the Mormons and may also explain the apparent association of polyposis with HLA A2 and B44 studied by Terasaki and Lynch and by Julia Bodmer and co-workers (Bodmer et al, 1985).