Describe Familial Adenomatous Polyposis in detail.

The Concept

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition caused by a mutation in the APC tumour-suppressor gene (chromosome 5). Its hallmark is the development of hundreds to thousands of adenomatous polyps carpeting the colon and rectum, beginning in adolescence. It is the archetypal example of an inherited colorectal cancer syndrome and demonstrates the adenoma-carcinoma sequence at its most dramatic.

The Cancer Risk

Because each of these numerous adenomas can progress to carcinoma, the risk of colorectal cancer approaches 100% by around the age of 40 if the colon is not removed. This near-certainty of malignancy is what makes FAP a prophylactic surgical disease — the colon is removed before cancer inevitably develops.

Screening & Management

Management centres on identification and prevention. Affected families undergo genetic testing, and gene carriers begin surveillance colonoscopy from their early teens. The definitive treatment is prophylactic surgery — total colectomy or proctocolectomy, often with an ileo-anal pouch — performed once polyps appear, to remove the organ at risk. Upper GI surveillance is also needed because of duodenal and ampullary adenomas.

Associated Syndromes

Two named variants are worth knowing: Gardner's syndrome (FAP with osteomas, desmoid tumours and epidermoid cysts) and Turcot's syndrome (FAP with central nervous system tumours). These extracolonic features can be the clue to the underlying polyposis.

Contrast with LYNCH Syndrome

It is worth contrasting FAP with the other major hereditary colorectal cancer syndrome, HNPCC (Lynch syndrome): Lynch is caused by mismatch-repair gene defects, produces few polyps (not thousands) but a high risk of colorectal (often right-sided) and extracolonic cancers (endometrial, ovarian). FAP is polyp-count driven and APC-based; Lynch is repair-defect driven — a distinction examiners frequently probe.

The Bottom Line

FAP is an autosomal-dominant APC-gene polyposis with near-certain colorectal cancer, managed by genetic testing, surveillance and prophylactic colectomy, with Gardner's and Turcot's as its named variants.

A Note on Chemoprevention & Timing

In FAP the timing of prophylactic surgery is judged by the polyp burden on surveillance, balancing cancer prevention against operating on a young person; NSAIDs/COX-2 inhibitors have been studied to slow polyp growth but do not replace colectomy. Lifelong surveillance of the retained rectum (if a pouch is not formed) and of the upper GI tract continues after surgery.

Colorectal cancer is certain by 40 without prophylactic surgery.

• FAP = autosomal dominant, APC tumour-suppressor gene mutation (chromosome 5).
• Hundreds–thousands of colorectal adenomatous polyps from adolescence.
• ~100% risk of colorectal cancer by ~40 if untreated → a prophylactic surgical disease.
• Genetic testing + surveillance colonoscopy from the teens; prophylactic (procto)colectomy ± ileo-anal pouch; upper-GI surveillance (duodenal/ampullary tumours).
• Variants: Gardner's (osteomas, desmoids) and Turcot's (CNS tumours).