What is the APC gene? How does it affect the body?

The APC gene has long been widely known as a highly mutated tumor suppressor gene in colorectal cancer (CRC). The gene-generated APC protein is a negative regulator that controls beta-catenin levels. In addition, it interacts with E-cadherin, which is involved in cell adhesion. Mutations in the APC gene can lead to colorectal cancer. Changes in the APC gene produce truncated gene products. This leads to activation of the Wnt signaling pathway and altered activity of many other cellular processes.

content

• 1. What is the APC gene?
• 2. Function of APC . Protein
• 3. Health conditions associated with genetic changes in the APC . gene
• 4. APC Gene Test for Colorectal Cancer

1. What is the APC gene?

1.1 APC stands for Adenomatous polyposis coli

APC is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that can lead to tumors.

The human APC gene is located on the long arm (q) of chromosome 5; in the range q22.2 (5q22.2). The APC gene has been shown to contain an entry site inside the ribosome. APC gene modifiers have also been identified in all mammalian species for which complete genomic data are available.

1.2 Molecular position :

Base pairs 112,707,498 to 112,846,239; on chromosome 5  

The position of the APC gene on chromosome 5 is q22.2 .

1.3 Other names

• APC_HUMAN
• DP2
• DP2.5
• DP3
• FAP
• FPC
• GS
• PPP1R46
• WNT . signaling route modifier

2. Function of APC . Protein

Proteins produced by the APC gene play an important role in a number of cellular processes. It helps determine whether a cell can develop into a tumor.

The APC protein helps control:

• Frequency of division of a cell
• How it attaches to other cells in the tissue
• How cells polarize?
• Morphology of 3D . structures
•  Whether a cell moves in or out of tissue.

This protein also helps to ensure that the number of chromosomes in the cell is made correct. The APC protein accomplishes these tasks mainly through binding to other proteins. Especially those proteins involved in the process of binding and participating in cell signaling. The activity of a specific protein, beta-catenin, is controlled by the APC protein. Regulation of beta-catenin prevents genes that stimulate cell division from being turned on too often and prevents cells from overgrowing.

3. Health conditions associated with genetic changes in the APC . gene

3.1 Desmoid Tumor

Several mutations in the APC gene have been found in people with benign tumors called desmoid tumors. These rare tumors arise from connective tissue. They provide strength and flexibility to structures such as bones, ligaments, and muscles.

APC gene mutations often cause the formation of desmoid tumors in the abdomen. But these tumors can also appear in other parts of the body. Although APC-associated desmoid tumors are often associated with a form of colon cancer known as familial adenomatous polyposis ( FAP ). Mutations in the APC gene can cause tumors in people who do not have this inherited condition. APC gene mutations are found in about 10 -15 % of non-hereditary (sporadic) desmoid tumors.  

Gastric fibromas are associated with mutations in the APC . gene

Most APC gene mutations cause sporadic desmoid tumors resulting in an abnormally short APC protein. The shortened protein cannot interact with the beta-catenin protein. Thus preventing the breakdown of beta-catenin when it is no longer needed. Excess beta-catenin promotes uncontrolled cell growth and division. This allows the formation of desmoid tumors.

3.2 Familial adenomatous polyposis

More than 700 mutations in the APC gene have been identified in families with familial forms of adenomatous polyposis. Most of these mutations result in the production of an abnormally short, non-functional version of the APC protein. This short protein cannot prevent cell overgrowth. This leads to the formation of abnormal tumors (polyps) in the colon, which can become cancerous. The most common mutation in FAP is a 5-nucleotide loss in the APC gene. This mutation changes the sequence of amino acids in the APC protein. 

Familial adenomatous polyposis

Most people with FAP will develop colorectal cancer. But the number of polyps and the time frame in which they become cancerous depends on the location of the mutation in the APC gene. The location of the mutation also determines: is an individual with FAP predisposed to develop desmoid tumors?

3.3 Turcot's syndrome

Mutations in the APC gene are also responsible for a disorder ; called Turcot syndrome. It is closely related to familial adenomatous polyposis. Turcot syndrome is a combination of colorectal cancer with a type of brain tumor called medulloblastoma. About two-thirds of people with Turcot syndrome have a mutation in the APC gene.

A certain mutation in the APC gene (not related to Turcot syndrome) is found in about 6% of people of 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. This change was initially supposed to be harmless. However, it has now been shown to be associated with a 10% to 20% increased risk of colon cancer.

3.4 Stomach cancer 

Somatic mutations in the APC gene may be involved in the development of a small percentage of gastric cancers.

>> See more articles on rectal cancer to learn how to reduce the risk of the disease.

3.5 Neuropathy

Rosenberg et al. found that: APC directs cholinergic synapse aggregation between neurons. This is a finding that has implications for neurological diseases such as Alzheimer's disease, age-related hearing loss, and for some forms of epilepsy and schizophrenia.

3.6 Other diseases

• Primary nodular adrenal hyperplasia 
• Other cancers

4. APC Gene Test for Colorectal Cancer

APC . gene testing

This blood test can find a variant of the APC gene that makes some people more likely to develop FAP (familial adenomatous polyposis).

4.1 Situations where genetic testing is recommended:

• Having more than 10 colon polyps
• Colon polyps and other types of tumors
• You are of Ashkenazi Jewish descent. Your family has a history of colon cancer or polyps can become cancerous.

4.2 Meaning of the test

APC variant genetic testing does not check if you have cancer or polyps. It only looks for a specific variant in the APC gene that could put you at risk. The doctor may refer to the test result as “positive” or “negative”. Those words mean something different than you think.

4.3 “Positive” test results

It means you have a malfunctioning APC gene. That makes you more likely to get FAP than people who don't. But that doesn't mean you'll definitely get it. If you already have colon cancer or polyps, it can affect how often you need to be checked.

4.4 “Negative” results

Meaning you don't have that gene variant. Remember that the test does not check for every possible problem with this gene. This trial also did not look at other genetic problems that run in families with colon cancer. It only looks for the APC gene variant.

4.5 What to do if the result is “positive”?

If it is found that you have the APC gene variant, your doctor will likely recommend an annual colonoscopy. This is a test that allows your doctor to examine your intestines for cancer or polyps that may become cancerous.

If you've had colon cancer or polyps before, your doctor may recommend removal. 

As we all know, the APC gene participates in many signaling and cell attachment processes in the body. Mutations in the APC gene cause disturbances in the synthesis of APC proteins. It is the cause of many health problems, especially colorectal cancer. Testing for the APC gene can help us detect genetic changes that can cause this cancerous condition.

>> See more: What to eat with stomach ulcers?

Doctor Truong My Linh