Is colonoscopy recommended for parents with a family history of colorectal cancer and potential genetic risk of FAP?

Colonoscopy Screening for Parents with Family History of Colorectal Cancer and FAP Risk

Colonoscopy screening is strongly recommended for parents with a family history of colorectal cancer and potential genetic risk of FAP, with specific timing based on the type of polyposis syndrome identified through genetic testing. 1

Screening Recommendations Based on FAP Risk

For Classic FAP:

• Flexible sigmoidoscopy or colonoscopy should be performed every 1-2 years starting at age 10-12 years and continued lifelong in mutation carriers 1, 2
• Once adenomas are detected, annual colonoscopy should be performed until prophylactic colectomy is planned 2
• Surgery is indicated when there are large numbers of adenomas or adenomas showing high-grade dysplasia 1, 3

For Attenuated FAP (AFAP):

• Total colonoscopy (not just sigmoidoscopy) should be performed every 2 years starting at age 18-20 years and continued lifelong in mutation carriers 1, 3
• This approach is necessary due to the tendency toward right-sided colonic adenomas in AFAP 2
• Some patients with AFAP can be conservatively managed with colonoscopy every 1-2 years and polypectomy 1

For At-Risk Family Members Without Identified Mutations:

• Surveillance should be carried out every 2 years until age 40, every 3-5 years between 40-50 years, and may be discontinued at age 50 if no polyposis has developed 1
• If genetic testing is negative or uninformative, clinical surveillance should begin at an age 5-10 years earlier than the earliest diagnosis in the family 4

Genetic Testing Considerations

• Full germline genetic testing for FAP should include DNA sequencing and large rearrangement analysis of the APC gene 1, 2
• Germline testing of MUTYH can be initiated by screening for the most common mutations (G396D, Y179C) in Caucasian populations, followed by analysis of the entire gene in heterozygotes 1
• Genetic counseling should guide testing and considerations of colectomy 3

Important Clinical Considerations

• FAP is characterized by at least 100 adenomatous polyps in the colon and rectum, with a 100% lifetime cancer risk if left untreated 1
• The most important clinical feature of FAP is the development of cancer in one or more of the multiple colorectal adenomas at the mean age of 40 years 1
• At diagnosis, 60% of symptomatic FAP patients will already have colorectal cancer, highlighting the importance of early screening 1
• In approximately 30-40% of FAP cases, there is no family history, suggesting a de novo mutation origin 2, 5

Screening for Extracolonic Manifestations

• Gastroduodenal endoscopy using both front and side-view scopes should be performed every 5 years until adenomas are detected 1, 3
• Screening for extracolonic manifestations should start when colorectal polyposis is diagnosed or at age 25-30 years, whichever comes first 1, 3
• Annual cervical ultrasonography is recommended for thyroid cancer screening in FAP patients 3

Caution and Pitfalls

• Early-onset disease can occur in some families, with polyps developing in childhood and even colorectal cancer in adolescence 6, 7
• FAP may initially present with vague abdominal complaints without any family history, requiring careful evaluation 5
• Some mutations (particularly between codons 1250 and 1464, especially codon 1309) are associated with a more severe form of FAP requiring more aggressive surveillance 2
• Even after prophylactic colectomy, ongoing surveillance is necessary as patients remain at risk for other manifestations of the disease 4, 8

Post-Surgical Surveillance

• After colorectal surgery, surveillance of the rectum or pouch should be carried out every 6-12 months if rectal tissue remains 1
• For patients with ileoanal pouch, surveillance should be performed every 6 months to 5 years depending on polyp burden 1, 4