Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Major Genetic Syndromes
Table 10. Clinical Practice Guidelines for Colon Surveillance of BiallelicMYH-Associated Polyposis (MAP) continued...
The clinical phenotype of monoallelic MYH mutations is less well characterized with respect to incidence and associated clinical phenotypes, and its role in pathogenesis of polyposis coli and colorectal carcinoma remains in dispute. Approximately 1% to 2% of the general population carry a deleterious mutation in MYH.[5,135,137] A 2011 meta-analysis found that monoallelic MYH mutation carriers are at modest increased risk of CRC (odds ratio [OR], 1.15; 95% CI, 0.98–1.36); however, given the rarity of monoallelic mutation carriers, they account for only a trivial proportion of all CRC cases. Although some studies have suggested screening these individuals on the basis of this modest increase in risk, others have suggested following screening recommendations for the general population.
MMR genes may interact with MYH and increase the risk of CRC. An association between MYH and MSH6 has been reported. Both proteins interact together in base excision repair processes. A study reported a significant increase of MSH6 mutations in monoallelic MYH mutation carriers with CRC compared to noncarriers (11.5% vs. 0%; P = .037).
Mut Y Homolog
The Mut Y homolog gene, which is also known as MUTYH and MYH, is located on chromosome 1p34.3-32.1. The protein encoded by MYH is a base excision repair glycosylase. It repairs one of the most common forms of oxidative damage. Over 100 unique sequence variants of MYH have been reported (Leiden Open Variation Database). A founder mutation with ethnic differentiation is assumed for MYH mutations. In Caucasian populations of northern European descent, two major variants, Y179C and G396D (formerly known as Y165C and G382D), account for 70% of biallelic mutations in MYH-associated polyposis patients, and 90% of these patients carry at least one of these mutations. Biallelic MYH mutations are associated with a 93-fold excess risk of CRC with near complete penetrance by age 60 years.
Oligopolyposis is a popular term used to describe the clinical presentation of a polyp count or burden that is greater than anticipated in the course of screening in average-risk patients but that falls short of the requirement for a diagnosis of FAP. Thus, oligo-, Greek for few, can mean different things to different observers. While conceding a lack of consensus on the matter, the National Comprehensive Cancer Network (NCCN) committee on CRC screening suggests an AFAP diagnosis is worth considering when 10 to 100 adenomas are present. It will be used here to describe the circumstance in which the polyp count (generally adenoma) is large enough, with or without any attendant family history, to raise in the mind of the endoscopist the possibility of an inherited susceptibility.