Colon Cancer Genetics - Cormier Flashcards
5% of colorectal cancer comes from hereditary syndromes and the other 95% is sporadic
2 pathways are involved in both of these forms: APC and mismatch repair (MMR).
Describe what APC and MMR involve?
APC pathway:
- Involves chromosomal instability (CIN)
- 30% survival
- often p53 loss
MMR:
- Involves microinstability
- 90% survival
What % of CRC could be prevented by early adenoma detection?
80%
What is one of the big benefits of CT colonography over endoscopic exam?
non-colonic lesions can be detected at the same time.
Most other advantages go to endoscope
Name a few dietary factors increasing CRC risk:
Red meat, omega 6, trans fats, processed meats, EtOH, low Ca and folate,
Name a few dietary factors decreasing CRC risk:
fish oils, omega 3, fruits and veggies, soy, fiber, folate, Ca, garlic, vit A,C,D,E, favinoids
What is the cancer-involved signaling system controlled by APC?
The WNT signaling pathway
If a CRC patient has this mutation, cetuximab and panitumumab will be ineffectives for their treatment:
K-Ras mutation
Autosomal dominant APC/CIN mutation causing thousands of colon colyps by the age of 15
Familial Adenomatous Polyposis (FAP)
What exactly is MIN, microsatellite instability?
small errors in DNA replication that are normally repaired by MMR enzymes. When MMRs are defective, there is slippage at DNA repeat sites, increasing size of repeat regions
Microsatellites are short repeat sequences, expansions or contractions in them can indicate MIN
Hereditary syndrome of MMR/MIN. Autosomal dominant, inherited as a single copy like FAP, then 2nd hit must occur for CRC to occur. What’s the syndrome?
Lynch Syndrome, aka HNPCC.
high risk for other cancers, more common in consanguineous populations, early onset
First line CRC therapy?
5-FU and thymidilate synthase
