Hereditary colorectal cancer: FAP and Lynch syndrome

Topic

Two inherited conditions explain much about colon cancer: one fills the colon with hundreds of polyps, the other breaks DNA spell-checking.

Updated Nov 12, 2026

Key points

FAP: autosomal dominant APC (Wnt pathway); at least a hundred adenomas; cancer in all untreated patients, often before thirty; prophylactic colectomy.
FAP extra-colonic: duodenal and ampullary adenomas, fundic gland polyps, congenital hypertrophy of the retinal pigment epithelium.
Gardner syndrome: FAP with osteomas, desmoid tumours, epidermal cysts and thyroid tumours; Turcot: FAP with brain tumours (medulloblastoma).
MUTYH-associated polyposis: autosomal recessive base-excision repair defect; fewer polyps, later onset.
Lynch syndrome: autosomal dominant, mostly MSH2 or MLH1; microsatellite instability; right colon, mucinous, lymphocyte-rich tumours.
Lynch cancers outside the colon: endometrium (most common), ovary, stomach, small bowel, urinary tract, hepatobiliary tree, brain, skin.

What it is

Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (Lynch syndrome) are the best-known inherited colon cancer syndromes, and each models a pathway that sporadic cancers also use. FAP is caused by germline APC mutation and produces hundreds to thousands of adenomas in adolescence; cancer is certain without colectomy. Lynch syndrome is caused by germline mutation in a mismatch-repair gene; patients have few polyps but develop right-sided colon cancer, endometrial cancer and other tumours at younger ages than usual.

Step by step

FAP: one APC allele is inherited faulty in every colonic cell.
A second hit in any crypt removes APC, β-catenin accumulates and Wnt targets drive growth: an adenoma.
Lynch: one mismatch-repair allele is inherited faulty.
Loss of the second allele causes errors at microsatellites to accumulate up to a thousandfold.
Mutations in microsatellite-containing genes (TGFBR2, BAX) drive rapid progression to cancer.

Inherited colorectal cancer syndromes

Syndrome	Gene	Inheritance	Polyps	Key features
Classic FAP	APC	Autosomal dominant	Hundreds to thousands of adenomas	Cancer by forty to fifty if untreated; retinal pigment hypertrophy
Gardner syndrome	APC	Autosomal dominant	As FAP	Osteomas, desmoids, epidermal cysts, dental anomalies
Turcot syndrome	APC (or mismatch repair)	Autosomal dominant	As FAP	Medulloblastoma (APC) or glioblastoma
MUTYH-associated polyposis	MUTYH	Autosomal recessive	Fewer than a hundred; serrated polyps too	Later cancer than FAP
Lynch syndrome (HNPCC)	MSH2, MLH1, MSH6, PMS2	Autosomal dominant	Few	Early right-sided cancer; endometrial cancer

Clinical notes

Tumours are screened for mismatch-repair protein loss by immunohistochemistry to find Lynch families.
Lynch syndrome accounts for a few percent of all colorectal cancers, making it the commonest inherited form.

Test yourself

Think of the answer, then tap the question to see it.

Which gene is mutated in familial adenomatous polyposis, and which pathway does it control?

APC, a negative regulator of β-catenin in the Wnt signalling pathway.

What molecular signature marks Lynch syndrome tumours?

Microsatellite instability from loss of DNA mismatch repair (most often MSH2 or MLH1).

Which extra-colonic cancer is most common in Lynch syndrome?

Endometrial carcinoma.

What extra-intestinal lesions define Gardner syndrome?

Osteomas, desmoid tumours, epidermal cysts and dental anomalies, with thyroid tumours, on top of FAP.

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Connections

← All of general pathology

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: Familial adenomatous polyposis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Lynch syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.