What is the most common location of colorectal cancer in Familial Adenomatous Polyposis (FAP) and Attenuated Familial Adenomatous Polyposis (AFAP)?

Most Common Location of Colorectal Cancer in FAP and AFAP

In classical FAP, colorectal cancer develops throughout the colon and rectum, while in AFAP, colorectal cancer is often localized in the proximal (right) part of the colon. 1

Classical FAP

• Classical FAP is characterized by the development of hundreds of colorectal adenomas during childhood and adolescence 1
• Without surgical intervention, FAP patients almost inevitably develop colorectal cancer by the mean age of 40-50 years 1
• The severity of colonic polyposis correlates with the site of the mutation in the APC gene 1
• Colorectal cancer in classical FAP tends to be distributed throughout the colon and rectum, with no specific predilection for a particular segment 1
• CRC before the age of 10 years is extremely rare, with incidental cases reported between ages 11 and 15 years 1
• The risk of rectal adenomas remains after colectomy, and there is a risk of adenomas and even cancer in the pouch after proctectomy 1

Attenuated FAP (AFAP)

• AFAP is characterized by fewer adenomas (typically 10-99) and later onset of disease compared to classical FAP 1
• The mean age at diagnosis of CRC in AFAP is about 10-15 years later than in classical FAP 1
• In contrast to classical FAP patients, AFAP patients may develop only a few adenomas in the right part of the colon 1
• Colorectal cancer in AFAP is often localized in the proximal (right) part of the colon 1, 2
• This right-sided predominance is an important clinical distinction that affects surveillance and surgical planning 1

MUTYH-Associated Polyposis (MAP)

• MAP is characterized by bi-allelic mutations in the MUTYH gene and presents with an attenuated polyposis phenotype 1
• Similar to AFAP, CRC in MAP is often localized in the proximal part of the colon 1
• CRC due to bi-allelic MUTYH mutations before the age of 30 years is extremely rare 1
• Bi-allelic mutation carriers may develop only a few adenomas, primarily in the right colon 1

Clinical Implications for Surveillance and Management

• The location of polyps and cancer risk affects the choice of surgical approach 1
• For classical FAP with diffuse polyp distribution, total proctocolectomy with ileal pouch-anal anastomosis is often recommended 1
• For AFAP with predominantly right-sided polyps, colectomy with ileorectal anastomosis may be considered in selected cases 1
• The decision on the type of surgery depends on many factors including the age of the patient, the wish to have children, the risk of developing desmoids, the site of the mutation in the APC gene, and the severity of rectal polyposis 1
• Colonoscopic surveillance should be tailored based on the expected distribution of polyps - for AFAP, special attention should be paid to the right colon 1, 2

Genetic Considerations

• The position of APC mutations correlates with the clinical presentation and polyp distribution 1, 3
• Mutations in the 5' and distal 3' portion of the APC gene are associated with AFAP and its characteristic right-sided predominance 1
• Understanding the genotype-phenotype correlation helps predict the likely location of polyps and cancer risk 3