Germline mutations of the adenomatous polyposis coli (APC) gene and the mutY homolog (MYH) genes predispose individuals to develop multiple colorectal adenomas, which frequently lead to carcinomas. The APC gene is a tumor suppressor gene believed to modulate the ß-catenin protein, which regulates cell signal transduction and growth. The MYH gene is thought to be an important part of the base excision repair (BER) pathway, which allows for repair of DNA mutations caused by oxidative damage to cells.

	The APC gene controls cellular growth and proliferation. The MYH gene repairs DNA damage caused by oxidation.

APC GENE
By inhibiting the ß-catenin protein, the APC gene controls cellular growth and proliferation. Nearly all familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) diagnoses are due to a germline mutation in the APC gene. Located on the long arm of chromosome 5, the APC gene consists of 15 exons of DNA, numbered in order from 5' (beginning of the gene) to 3' (end of the gene). Individuals with FAP or AFAP have one nonfunctioning copy of the APC gene in their germline. When the remaining working copy is inactivated by a deleterious mutation, the gene loses its ability to control cell replication, leading to uncontrolled cellular growth. It is thought that the location of the mutation on the APC gene may contribute to the different phenotypes seen in FAP and AFAP.

MYH GENE
As a "caretaker" gene, MYH is responsible for repairing DNA damage caused by reactive oxygen species that are generated during aerobic metabolism. When inherited mutations occur in MYH, damage accumulates in the APC gene and its function is impaired. Thus, the effects of inherited MYH mutations are similar to those seen with inherited APC mutations. The MYH gene is located on the short arm of chromosome 1 and consists of 16 exons of DNA. Individuals with MAP have inherited mutations in both copies of their MYH genes (one from each parent)-this may be referred to as "biallelic MYH mutations."

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