carcinoma of the colorectal Flashcards
4 types of polyps
neoplastic
haemartomatous
inflammatory
unclassified: hyperplastic
which type of polyp has the highest risk of malignancy
neoplastic
what are the solitary and multiple types of neoplastic polyps
solitary=adenoma -tubular -tubulovillous -villous multiple=FAP
what are the solitary and multiple haemartomatous polyps
solitary -juvenile polyp -peutz-jeghers polyp multiple -juvenile polyposis -peutz jeugher -cronkhite-canada -cowden's disease
what are the solitary and multiple inflammatory polyps
solitary=
- benign lymphoid polyps
- pseudo-polyps
multiple
- benign lymphoid polyposis
- pseudo-polyposis (UC)
unclassified types of polyps
solitary
- metaplastic
- hyperplastic
- lipoma
- neurofibroma
multiple
- multiple metaplastic polyps
- MAP (MYH assoc. polyposis)
colorectal adenoma polyps risk of malignancy
- tubular
- tubularvillous
- villous: most
evidence for adeno-carcinoma sequence
- high prevalence of adenomas in patients with high cancer rate
- fap
- similar distribution colon and rectum
- age specific peak
- focci of carcinoma detected adenoma
- focci of adenoma common in early carcinoma
- future cancer risk relates to total adenoma load
- polypectomy assoc. with reduced cancer incidence
genes involved in first stage of adeno carcinoma sequence
- first hit to the APC gene ie hereditary
- second hit to the APC gene-somatically
- beta catenin signalling= mucosa at risk- methylation abnormalities
where is APC gene located
APC at 5q21
gene involved in formation of adenoma in adenocarcinoma sequence
- kRAS-oncogene
genes involved in formation of adenocarcinoma
TP53
LOH
SMAD 2 and 4- tumour suppressor
gene involved in additional mutations
telomerase
m:f for colon and rectum cancer
f>m for colon
m>f for rectum
age peak for colorectal cancer
75-79
what number is it for cancer causes of death
2nd
risk factors for colorectal cancer
western diet -red meat -high fat -low in fibre lifestyle -smoking -exercise -beer (rectal cancer) IBD -pan UC 30% at 30 yrs -CD genetic disposition -HNPCC -FAP -PJS -JPS
what is FAP and inheritance
autosomal dominant with penetrance
-inactivating mutation of APC gene (5q21) adenomatous polyposis coli gene
-benign adenomas but risk malignancy
1% population
amsterdam criteria for HNPCC
hereditary non polyposis colorectal cancer
- > 3 family members with histologically proven colorectal cancer
- one relative a first degree relative to the other two
- > 2 generations affected
- age at onset <50 in at least one family member
- uterine cancer in one or more relatives acceptable as part of a 3 member family
mutations in dna mismatch repair gene
msh2
mlh1
msh6
pms2
lifetime risk for mismatch mutation repair genes
80 males
30% females
hnpcc genetics
autosomal dominant 1.microsatellite instability -defect in MLH1 promoter -cells accumulate -keep the repeating defect often in CAT cytosine adenine tandem microsatellite gene
types of microsatellite mutations
missense: diff protein
nonsense: stop
insertion
deletion
duplication
frameshift: non functional
repeat expansion: nucleotide repeats
colorectal cancer presentation
obstruction perforation bleeding localised pain altered bowel habits rectal bleeding colicky pain anaemia anorexia weight loss malaise flactulence
