Colon Cancer and Carcinogenesis Flashcards
familial adenomatous polyposis syndrome
adenocarcinoma of colon with mixed glandular and neuroendocrine differnetiation
multifocal adencarcinomas
tubular ademonas
hereditary, dominant, 100% risk factor
pts get cancer very young, younger than sporadic cancer
what goes wrong in pts w/ FAP?
mutations in the APC gene- causes adenoma
eventually ademonas go on to form carcinomas as they acquire independent mutations
functions of APC
binds B-catenin- which moves to the nucleus and drives proliferation
important in colonic stem cells
only found in junctions in epithelium normally
w/ mutated APC, free B-catenin is allowed to go to nucleus and drive proliferation
how does mutated APC affect the colonic crypts
mutated APC causes increased crypts, length, and branching of colonic crypts. structure and differentiation is maintained. additional mutations cause more heterogenous branching
affects of APCs on colonic cancer
prevent polyps
lynch syndrome
mismatch repair gene
patients have less polyps and they occur later in life than FAP
80% risk factor in lynches
occurs in right colon
autosomal dominant
most often causes cancer in colon or endometrium
guidelines for diagnosis of lynch syndrome
3 or more relatives w/ associated cancer
2 or more successive generations affected
1 or more relatives diagnosed before age 50
how does lynch syndrome occur?
mismatch repair gene defects
- MSH2 and MLH1 are essential proteins for the mismatch repair complex. if they are mutated, mismatch repair does not occur and can lead to cancer.
- transcribed along w/ EPCAM. mutations in EPCAM can cause polymerase to miss MSH 2 gene
- if MLH1 becomes hypermethylated, mismatch repair doesnt occur
leads to elongation or shortening of microsatellite repeats- slippage
how often should carriers of MLH1 or MSH2 mutations be screened?
colonoscopy every 1-2 years
