Clinical Guidance
APC-associated polyposis conditions include classic familial adenomatous polyposis (FAP), attenuated FAP, and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP In individuals with classic FAP, colorectal adenomatous polyps begin to appear in the second and third decade; the average age of polyp diagnosis is 16 years (range 7-36 years) . By age 35 years, 95% of individuals with FAP have polyps. Once they appear, the polyps rapidly increase in number; when colonic expression is fully developed, hundreds to thousands of colonic adenomatous polyps are typically observed. Without colectomy, colorectal cancer (CRC) is essentially inevitable. The average age of CRC diagnosis in untreated individuals is 39 years (range 34-43 years); 7% of untreated individuals with FAP develop CRC by age 21 years, 87% by 45 years, and 93% by 50 years. Although rare, asymptomatic individuals in their 50s have been reported. Inter- and intrafamilial phenotypic variability are common . Attenuated FAP is characterized by fewer colonic polyps (average of 30 polyps) than classic FAP but a significant risk for CRC. According to the international collaborative study by , attenuated FAP was clinically defined as individuals with ≤100 colorectal adenomatous polyps at age ≥25 years. Polyps tend to occur more proximally in the colon than in classic FAP. The average age of CRC diagnosis in individuals with attenuated FAP is 50 to 55 years – ten to 15 years later than in classic FAP, but earlier than in those with sporadically occurring CRC . The cumulative risk for CRC by age 80 years in attenuated FAP is estimated at 70% . Other Features Variably Present in FAP Table 2. Lifetime Risk for Extracolonic Cancer in Familial Adenomatous Polyposis
Site | Type of Cancer | Lifetime Risk for Cancer |
|---|
Small bowel: duodenum (most often periampullary region) | Adenocarcinoma, carcinoma | 4%-12% |
Small bowel: distal to the duodenum | Carcinoma | Rare |
Pancreas | Adenocarcinoma | ~1% |
Thyroid | Papillary thyroid carcinoma | 1%-12% |
CNS | Usually medulloblastoma | ~1% |
Liver | Hepatoblastoma | 1.6% |
Bile ducts | Adenocarcinoma | Low, but |
Stomach | Adenocarcinoma | 1.3% in Western cultures since 2016 Small-bowel polyps and cancer. Adenomatous polyps of the duodenum, observed in 50%-90% of individuals with FAP, are commonly found in the second and third portions of the duodenum and to a variable degree in the jejunum or ileum . |
Source: GeneReviews — "APC-Associated Polyposis Conditions"
