APC and colorectal carcinoma: The identification of the missense variant, APC I1307K, carried by ~6% of Ashkenazi Jews and conferring around a two-fold increase in risk of CRC [42] and the more recent discovery of the functional promoter variant -93G>A of MLH1, shown to predispose to microsatellite unstable CRC [43], represent rare successes of this approach.