Which are the causes of Familial Adenomatous Polyposis?

Familial Adenomatous Polyposis (FAP) is a rare genetic disorder characterized by the development of numerous polyps in the colon and rectum. These polyps are benign initially but have the potential to become cancerous over time if left untreated. FAP is primarily caused by mutations in the adenomatous polyposis coli (APC) gene, which is responsible for suppressing tumor growth.

1. Genetic Mutations: The most common cause of FAP is an inherited mutation in the APC gene. This gene normally helps regulate cell growth and division, but when it is mutated, it fails to control the growth of polyps in the colon and rectum. FAP follows an autosomal dominant inheritance pattern, meaning that a person only needs to inherit one copy of the mutated gene from either parent to develop the disorder.

2. De Novo Mutations: In some cases, individuals with FAP have no family history of the disorder. This occurs when a new mutation in the APC gene arises spontaneously during the formation of reproductive cells or early embryonic development. These de novo mutations can be passed on to future generations.

3. Variant Forms: While mutations in the APC gene are the primary cause of FAP, there are also variant forms of the disorder caused by mutations in other genes. These include attenuated FAP (AFAP) and MUTYH-associated polyposis (MAP). AFAP is characterized by fewer polyps and a later onset compared to classic FAP. MAP is caused by mutations in the MUTYH gene, which is involved in DNA repair.

4. Genetic Testing: Genetic testing can be performed to identify mutations in the APC gene or other related genes associated with FAP. This can help confirm a diagnosis, assess the risk of developing polyps or cancer, and guide appropriate management and treatment options.

5. Other Risk Factors: While FAP is primarily caused by genetic mutations, there are certain risk factors that can increase the likelihood of developing polyps or cancer. These include a family history of FAP or colorectal cancer, certain lifestyle factors such as smoking and excessive alcohol consumption, and certain medical conditions like inflammatory bowel disease.

Early detection and intervention are crucial in managing FAP. Regular screenings, such as colonoscopies, are recommended for individuals with FAP to monitor and remove polyps before they become cancerous. Surgical removal of the colon may be necessary in some cases to prevent the development of colorectal cancer.