APC

The APC gene provides instructions for making the APC protein, which plays a critical role in several cellular processes that determine whether a cell will develop into a tumor. The APC gene is a tumor suppressor gene, which means that it regulates the cell division cycle by keeping cells from growing and dividing too fast or in an uncontrolled way. The APC protein helps control how often a cell divides, how it attaches to other cells within a tissue, and whether a cell moves within or away from a tissue. This protein also helps ensure that the number of chromosomes in a cell is correct following cell division. The APC protein accomplishes these tasks mainly through association with other proteins, especially those that are involved in cell attachment and signaling.

familial adenomatous polyposis - caused by mutations in the APC gene

More than 700 mutations in the APC gene have been identified in families with the classic and attenuated types of familial adenomatous polyposis (FAP). Most of these mutations lead to the production of an abnormally short, nonfunctional version of the APC protein. This short protein cannot suppress the cellular overgrowth that leads to the formation of polyps, which can become cancerous. The most common mutation in familial adenomatous polyposis is a deletion of five building blocks of DNA (nucleotides) in the APC gene. This mutation changes the sequence of the building blocks of proteins (amino acids) in the resulting APC protein.

Although most people with mutations in the APC gene will develop colorectal cancer, the number of polyps and the time frame in which they become malignant depend on the location of the mutation in the gene.

other cancers - increased risk from variations of the APC gene

Mutations in the APC gene are also responsible for a disorder called Turcot syndrome, which is closely related to familial adenomatous polyposis. Turcot syndrome is an association of colorectal cancer with a type of cancerous brain tumor called a medulloblastoma. Approximately two-thirds of people with Turcot syndrome have mutations in the APC gene.

One mutation in the APC gene is found in approximately 6 percent of people with Ashkenazi (eastern and central European) Jewish heritage. This mutation replaces the amino acid isoleucine with the amino acid lysine at position 1307 in the APC protein (written as Ile1307Lys or I1307K). This change was initially thought to be harmless, but has been shown to be associated with a 10 percent to 20 percent increased risk of colon cancer.

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations that inactivate the APC gene may also be involved in the development of a small percentage of stomach (gastric) cancers.