Table 2.
Causative genes and clinical manifestations of inherited polyposis syndrome
| Syndrome | Causative gene | Clinical manifestations | Lifetime syndrome risk of associate neoplasmsa (%) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Colon | Stomach | Small bowel | Pancreas | Breast | Endometrial | Ovary | Urinary | Thyroid | Others | |||
| FAP | APC (AD) | Benign soft tissue tumor, CHRPE | 90 (69b) | 2–5 | 5–20 | 2–5 | 5–20 | Desmoid, MB | ||||
| MAP | MUTYH (AD) | CRC-proximal colon, mucin, LC infiltration | 43–63 | Less common than those in FAP, otherwise similar spectrum to LS | ||||||||
| PPAP | POLE, POLD1 (AD) | LS-like phenotype in a minority | 70 | 9.5 | 12 | IR | ||||||
| Sessile polyposis | RNF43 (AD) | ≥5, >rectum (≥2, ≥10 mm), ≥20 (≥5, >rectum) | 20 | Undetermined | ||||||||
| Peutz-Jeghers | STK11 (AD) | Mucocutaneous pigmented macules | 40 | 5–20 | 2–5 | 5–20 | 50 | 10 | 20 | |||
| JP | SMAD4, BMPR1A (AD) | ≥5, extrabowel JP, family history | 20–40 | 5–20 | ||||||||
| PHTS | PTEN, PTCH (AD) | Including BRRS, CS, GS, PS; Upper GIc | 9 | 85 | 28 | 34 | 35 | Melanoma | ||||
| HMPS | SCG5/GREM1 (AD) | Adenoma, serrated/inflammatory polyp | Undetermined | |||||||||
FAP, familial adenomatous polyposis; AD, autosomal dominant; CHRPE, congenital hypertrophy of retinal pigment epithelium; MB, medulloblastoma; MAP, MUTYH-associated polyposis; CRC, colorectal cancer; LC, lymphocyte; LS, Lynch syndrome; PPAP, polymerase-proofreading-associated polyposis; IR, increased rate; JP, Juvenile polyposis; PHTS, PTEN hamartoma tumor syndrome; BRRS, Bannayan-Riley-Ruvalcaba syndrome; CS, Cowden syndrome; GS, Gorlin syndrome; PS, Proteus-like syndromes; GI, gastrointestinal; HMPS, hereditary mixed polyposis.
Lifetime syndrome risks mostly based on the American College of Gastroenterology Guideline of Hereditary Gastrointestinal Cancer Syndromes (2015; https://gi.org/guidelines/) and included refer-ences; PPAP based on the National Study of Colorectal Cancer Genetics (2013), UK; PHTS based on the International Cowden Consortium (2012).
Risk in the parenthesis indicates lifetime risk (%) in attenuated FAP.
The most common upper GI lesions are esophageal glycogenic acanthosis (37%), gastric hamartomatous polyps (47%), and duodenal hamartomatous polyps (20%).