Familial adenomatous polyposis (APC and MUTYH genes)

Familial adenomatous polyposis (FAP) is a pathology characterised by the appearance, in the second decade of life, of hundreds or thousands of adenomatous polyps in the rectum and colon area that, if left untreated, can lead to colorectal cancer (CRC).

Classic FAP is inherited in an autosomal dominant manner and results from a copy of a pathogenic variant in the APC gene. In some cases, it may be due to alterations in another gene, called MUTYH, causing recessively transmitted polyposis, which is characterised by a slightly increased risk of developing CRC and by the presence of polyps/adenomas in the upper and lower gastrointestinal tract.

FAP has an incidence of 1 case per 8,300 people, affects both sexes equally, and accounts for less than 1% of CRC cases. The prevalence in the European Union is estimated at 1 case per 11,300-37,600 inhabitants.

Most patients are asymptomatic for years until the adenomas are large and numerous, causing rectal bleeding or even anemia. Generally, cancer begins to develop 15-20 years after the appearance of the polyps. Nonspecific symptoms include constipation or diarrhea, abdominal pain, palpable abdominal masses, and weight loss. FAP may present with some extraintestinal manifestations: osteomas or benign cancers, dental anomalies, congenital hypertrophy of the retinal pigment epithelium, desmoid tumors or benign cancers in connective tissues, and extracolonic cancers.

There is a less aggressive variant, attenuated FAP, which is characterized by a lower number of pólipids (typically between 10 and 100), appearance of adenomas at a later age, and a lower risk of cancer.

The main goals of FAP management are CRC prevention and a good quality of life. Patients with classic FAP associated with PCa have a nearly 100% risk of developing CRC, although this risk is markedly reduced when they enter a screening program and are treated. Therefore, prophylactic colorectal surgery is usually performed at an early age and is followed up with lifelong follow-up with perioperative endoscopies. Revisions are necessary as adenomas arise and grow in the retained rectum or ileal pouch.

Current CRC risk surveillance measures in patients with MUTYH-associated FAP include a high-quality colonoscopy every 1-2 years, beginning no later than age 25-30 years.