Abstract

We summarize the genetic and clinical features of the colorectal adenomas and cancers that occur in MYH-associated polyposis (MAP). MAP results from biallelic germline mutations in the base excision repair gene, mutY homologue (MYH). MAP has a phenotype that is often indistinguishable from classical or attenuated familial adenomatous polyposis (FAP), but the former is inherited as a recessive condition, whereas the latter is a dominantly inherited disease caused by germline mutations of the APC gene. MYH mutations seem to act by increasing the frequency of somatic APC mutations. MAP tumors may then progress to cancer along a distinct genetic pathway. MAP occurs in several different ethnic groups, the mutation spectrum appearing to differ among groups. It remains unknown, however, as to why carriers of MYH mutations specifically develop tumors of the gastrointestinal tract. In general, carriers of biallelic MYH mutations should be treated and followed up as for FAP patients with a similar phenotype. Relatives of MAP patients should be counseled as for any other recessive condition, although it remains possible that carriers of single mutations are at a modestly increased risk of colorectal cancer.