Colorectal cancer Flashcards
Epidemiology
3rd most common
3rd most deadly in US
Most >50 yrs
~25% fam hx
Genetics types
1) familial adenomatous polyposis
2) Gardner’s
3) Turcot’s
4) hereditary nonpolyptosis colorectal cancer
Genetics:
Familial adenomatous polyposis
AD mutation on APC gene on Ch 5q (polyp=5 letters) 2 hit hypothesis 100% progress to CRC Thousands of polyps; pancolonic, Always involve rectum (like UC)
Genetics:
Gardner’s
FAP+ osseous and soft tissue tumors
Congenital hypertrophy of retinal pigment epithelium
“Gardner has really dark retina”
Genetics:
Turcot’s
FAP+ malignant CNS tumor
Turcot=turban
Genetics:
HNPCC/Lynch
AD mutation of DNA mismatch repair genes
~80% progress to CRC
PROXIMAL colon always involved
Risk factors for CRC
IBD Tobacco use Large villous adenomas Juvenile polyposis syndrome Peutz-Jeghers
Presentation
site
Rectosigmoid > ascending > descending
Presentation:
ascending
Exophytic mass,
iron deficiency anemia*
weight loss
Presentation
descending
Infiltrating mass
partial obstruction
colicky pain
hematochezia*
Dx
Iron deficiency in male (>50 yrs) and
post menopausal females raise suspicion.
Screen >50 yrs of age with colonoscopy or stool occult
Apple core lesion on barium enema
CEA tumor markers: good for monitoring recurrence, not useful for screening.
Molecular dx of CRC
Two molecular pathways
1) Microsatellite instability (15%): DNA mismatch repair gene, sporadic and HNPCC syndrome
2) APC/beta-catenin (autosomal instability) pathway (85%)
Loss of APC=> K-ras => loss of p53
“AK-53”
Molecular characteristic
Loss of APC (to colon at risk): decreased intercellular adhesion, increased proliferation
KRAS (to adenoma): intracellular signal tranduction
Loss of p53 (to carcinoma): increased tumorigenesis.
