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Genetic mapping of a second locus predisposing to hereditary non-polyposis colon cancer. Nat Genet 1993; 5:279–282. 22. Strand M, Prolla TA, Liskay RM, Petes TD. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair [see comments] [published erratum appears in Nature 1994 Apr 7;368(6471);569]. Nature 1993; 365:274–276. 23. Bronner CE, Baker SM, Morrison PT, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer.
Thus, targeting screening and more intensive approaches to those at higher risk could improve the efﬁciency of such public health measures. Nontruncating Variants in the APC Gene As discussed earlier, the vast majority of truncating variants in the APC gene cause a polyposis phenotype with a high-penetrance colorectal cancer phenotype. However, in view of its central gatekeeper role, APC is a strong candidate contributing to colorectal cancer susceptibility through common genetic variation, and a number of nontruncating alleles associated with excess colorectal cancer risk have been described.
38 in the data from studies of 30 Barnetson and Dunlop populations living in the United States, while there was no effect for European populations. Nonetheless, components of the TGF signaling pathway constitute strong candidate genes in view of the antiproliferative and apoptosis-promoting role of TGFb. 2% to the total burden of colorectal cancer, greater than that of FAP and approaching that of HNPCC alleles. Loss of imprinting of the insulin-like growth factor II gene (IGF2) has been found in the normal colonic mucosa in around one-third of patients with colorectal cancer, a threefold excess in comparison to controls (164).