APC gene

APC gene- Familial Adenomatous Polyposis (FAP)

FAP is a colon cancer predisposition syndrome in which numerous precancerous polyps develop in the colon at a young age. Without colectomy (removal of the colon), colon cancer is inevitable. Other features of FAP are variably present and include osteomas, CHRPE, dental anomalies, polyps of the gastric fundus and duodenum, and desmoid tumors.  When extracolonic skin findings are noted in addition to the colon polyps, FAP is sometimes called Gardner Syndrome. Although rare, individuals with FAP are also at increased risk for cancers of the thyroid, central nervous system, liver, bile ducts, and adrenal gland.

Similarly, Attenuated FAP is a colon cancer predisposition syndrome in which numerous precancerous colon polyps develop around the age of 50. If left untreated, the risk for colon cancer in this condition is very high. Colon cancer in AFAP can be prevented through colectomy (surgical removal of the colon) once polyps become too numerous to manage with colonoscopy. Other features of AFAP are variably present and include osteomas, dental anomalies, polyps of the gastric fundus and duodenum, and desmoid tumors. Although rare, individuals with AFAP are also at increased risk for cancers of the thyroid, central nervous system, liver, bile ducts, and adrenal gland.

Both FAP and AFAP is inherited in an autosomal dominant manner; therefore each child of a person with AFAP is at 50% risk for having inherited the disease causing mutation. Due to the variability of onset of polyposis, the patient’s siblings and their offspring may still be at risk for the condition.

 

Recommendations for current and long term gastrointestinal screening for FAP were discussed.

  1.  Colonoscopy every year.
  2. Esophagogastroduodenoscopy (EGD) every 1-3 years to monitor for fundic gland polyps.
  3. Annual physical exam
  4. Palpation of the thyroid is also recommended.  Any suspicious thyroid lesions should be followed up by ultrasound and if abnormal, by biopsy.
  5. Following total colectomy, the patient will require endoscopic check-ups of either the remaining rectum or ileal pouch, depending on the type of surgery performed.  This is typically recommended every 1-3 years. EGD and thyroid cancer screening should also continue indefinitely.

For at risk relatives, surveillance should include:

Colonoscopy every 2-3 years beginning at 10-12 years of age. If colon polyps are detected, the recommendations for individuals known to have FAP are instituted as described above.

 

APC gene - I1307K

The APC I1307K mutation is a mutation of the APC gene that can lead to colorectal cancer.  Mainly found in Ashkenazi Jews, the mutation makes the gene unstable.  This makes it easy or the gene to continue to mutate, which may lead to colorectal cancer.  APC I1307K is inherited in an autosomal dominant manner; therefore each child of a person with APC I1307K is at 50% risk for having inherited the disease causing mutation. Due to the variability of onset of polyposis, the patient’s siblings and their offspring may still be at risk for the condition.  It is recommended that those with the mutation have a colonoscopy every five years beginning at the age of 40 or ten years prior to the youngest diagnosis of colorectal cancer in the family.

 

Resources

 

Genetics Home Reference: http://ghr.nlm.nih.gov/condition/familial-adenomatous-polyposis

Hereditary Colon Cancer Takes Guts http://www.hcctakesguts.org

http://www.hopkinscoloncancercenter.org/CMS/CMS_Page.aspx?CurrentUDV=59&CMS_Page_ID=4DD4642E-1A7E-4D78-8CCE-1977D805F54C

https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf