[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Gastrointestinal tract](https://durgical.com/en/general-pathology/areas/gi/) › Hereditary colorectal cancer: FAP and Lynch syndrome # 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](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) | APC | Autosomal dominant | Hundreds to thousands of adenomas | Cancer by forty to fifty if untreated; retinal pigment hypertrophy | | [Gardner syndrome](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) | APC | Autosomal dominant | As FAP | Osteomas, desmoids, epidermal cysts, dental anomalies | | [Turcot syndrome](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) | APC (or mismatch repair) | Autosomal dominant | As FAP | Medulloblastoma (APC) or glioblastoma | | [MUTYH-associated polyposis](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) | MUTYH | Autosomal recessive | Fewer than a hundred; serrated polyps too | Later cancer than FAP | | [Lynch syndrome (HNPCC)](https://durgical.com/en/conditions/lynch-syndrome/) | 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. ## Memory aid FAP floods the colon with polyps; Lynch lies low with few polyps but broken spell-check. ## 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. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/hereditary-colorectal-cancer-fap-and-lynch-syndrome/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Connections ## Related 6 - [Colonic adenomas and serrated lesions](https://durgical.com/en/general-pathology/colonic-adenomas-and-serrated-lesions/) - [Colorectal adenocarcinoma](https://durgical.com/en/general-pathology/colorectal-adenocarcinoma/) - [Gastric polyps](https://durgical.com/en/general-pathology/gastric-polyps/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) - [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/) - [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/) ## Related conditions 4 - [Colorectal polyps and hereditary polyposis syndromes (FAP, Lynch)](https://durgical.com/en/conditions/colorectal-polyps-and-hereditary-polyposis-syndromes/) - [Lynch syndrome (hereditary non-polyposis colorectal cancer)](https://durgical.com/en/conditions/lynch-syndrome/) - [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/) - [Gastric cancer](https://durgical.com/en/conditions/gastric-cancer/) [← All of general pathology](https://durgical.com/en/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](https://medlineplus.gov/genetics/condition/familial-adenomatous-polyposis/) (MedlinePlus, US National Library of Medicine, 2025); [Lynch syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/lynch-syndrome/) (MedlinePlus, US National Library of Medicine, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/hereditary-colorectal-cancer-fap-and-lynch-syndrome/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hereditary-colorectal-cancer-fap-and-lynch-syndrome/