Colon polyposis and hereditary colorectal cancer syndromes
Five inherited syndromes drive colorectal cancer risk through distinct genes and polyp biology: FAP and MUTYH-associated polyposis through adenomas, Lynch syndrome through mismatch-repair loss, and Peutz-Jeghers and juvenile polyposis through hamartomas. Each carries its own inheritance pattern, surveillance schedule, and threshold for surgery.
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What this article covers
- Overview
A family of inherited syndromes, not one disease: familial adenomatous polyposis (FAP), Lynch syndrome, MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome…
- Epidemiology
Lynch syndrome is the most common inherited CRC syndrome, accounting for about 3% to 4% of all colorectal cancers.
- Risk factors
A strong family cancer history is the single strongest clue: multiple relatives with colorectal or Lynch-associated cancers, cancer before age 50, or synchronous/metachronous tumors should trigger evaluation.
- Pathophysiology
FAP: biallelic APC inactivation (two-hit hypothesis).
- Clinical features
FAP: usually more than 100 adenomatous colon polyps beginning after puberty, plus supporting findings: duodenal/ampullary adenomas, gastric fundic gland polyps, desmoid tumors (especially…
- Differential diagnosis
Sporadic colorectal cancer: no polyposis phenotype, average-risk screening at age 45, no early-onset/multi-organ pattern.
- Diagnosis
No single criteria set covers the group; each syndrome is confirmed on its own terms.
- Management
First, direct all patients with a suspected or confirmed syndrome to genetic counseling before testing, and offer cascade germline testing to first-degree relatives once a pathogenic variant is…
- Complications
Colorectal cancer is the shared endpoint of unmanaged polyp burden across all five.
- Prognosis
Untreated classic FAP progresses to colorectal cancer in 100% of cases, average onset age 39, 93% cumulative risk by age 50; colectomy before cancer develops normalizes outcomes.
- Prevention
FAP/AFAP colon surveillance: classic FAP mutation carriers begin flexible sigmoidoscopy or colonoscopy at age 10 to 12, repeated every 1 to 2 years until colectomy; AFAP surveillance can be delayed to age 20 to 25 with colonoscopy.
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