GASTROENTEROLOGY ARTICLE OF THE WEEK
November 17, 2005
Doxey BW, Kuwada SK, Burt RW. Inherited polyposis syndromes: Molecular mechanisms, clinicopathology and genetic testing. Clin Gastroenterol Hepatol 2005;3:633-41.
1. Familial adenomatous polyposis syndrome (FAP):
a. If left untreated, cancer develops at a mean age of 39 years
b. The mutated APC gene can only be detected in colonic tissue
c. DNA sequencing of the APC gene is the preferred method to identify mutations
d. Persons with 20 or more adenomas should be tested for APC gene mutations
e. Colon cancer screening should begin at age 8 for FAP and age 18 for attenuated FAP
f. Genetic testing for FAP is performed using biopsies of colon adenomas.
g. Inheritance is autosomal-dominant
2. Juvenile polyposis syndrome:
a. Typically presents at age 18 with dozens to hundreds adenomatous polyps.
b. Rectal bleeding and anemia is a common presentation
c. Polyps are restricted to the colon
d. Patients with < than 5 hamartomatous polyps in the colon are classified as having sporadic JP and should undergo genetic testing
e. Dilated cystic spaces within the polyps are classic histologic findings
f. the genetic defect usually arises in chromosome 18q
g. individuals with multiple juvenile polyps should be tested for MADH4 and BMPR1A mutations
3. MutY human homologue (MYH)-associated polyposis:
a. is a syndrome of multiple colorectal adenomas and neoplasia with no identifiable germline APC gene mutation
b. patients present at a later age, with variable number of colon polyps
c. inheritance is autosomal-dominant.
d. genetic basis is a defect in a base excision repair gene in chromosome 1.
e. two most common mutations in the MYH gene are G382D and Y165C.
4. Cowden Syndrome (CS)
a. multiple hamartomas with a high risk of bilateral breast cancer and thyroid cancer.
b. autosomal recessive inheritance.
c. multiple facial trichilemmomas is a hallmark of this syndrome.
d. skin and mucous membrane involvement is present in <30% of cases.
e. GI hamartomas are most common in the stomach, colon and esophagus, presenting as glycogenic acanthosis in the esophagus.
f. GI cancer risk is very high in CS.
g. histologically, presence of neural tissue in the hamartomatous polyps is typical for CS.
5. Peutz-Jegher syndrome (PJS):
a. autosomal dominant syndrome with multiple hamartomatous polyps most often found in the
small bowel.
b. histologically, the muscularis mucosa extends within the mucosa of the polyp in an arborizing
pattern giving the impression of pseudoinvasion.
c. most common complications in PJS involves the small bowel due to intussusception,
obstruction and bleeding.
d. by age 65, over 90% of affected individuals will develop GI or extraintestinal cancers.
e. The mutation arises in chromosome 19p, in 50% of cases, the mutation is new and no family
members are affected.
f. Patients with suspected PJS should be tested for STK11 mutations.
True or False
6. APC alleles remain normal in sporadic colon cancer.
7. The APC gene is a tumor suppressor gene, both alleles must be damaged to allow for tumorigenesis.
8. Juvenile polyposis syndrome is not associated with increased risk of colon cancer.
9. In patients with the genetic defect for juvenile polyposis, screening should begin in the teenage years with upper and lower endoscopy.
10. The presence of STK11 mutation in families with PJS increase the risk of biliary adenocarcinoma.
11. Genetic defect in CS is in chromosome 10q23, PTEN gene.