Bowel cancer Flashcards
Risk factors
S: Surgery
A: Adenoma in large bowel
F: Family History
E: Environment
IBD and age
Migration to high risk population.
Food rich in meat and fat
Food rich in vegetables and fibre reduce cancer by increase faecal bulk
High fibre diet
Increase SCFA = promote healthy gut microbes = induce differentiation, arrest growth of cells and cause apoptosis
Increase stool bulk = reduce e transit time
Reduce secondary BA formation
Polyp
Protrusion into hollow viscus
Polyp pathological features
Hyperplastic - more goblet cells than normal mucosa
Tubular adenoma - test tube appearance
Villous adenoma - fingerlike
Tubulovillous adenoma
Dysplasia
Morphological features of cancer but no invasion
Low grade = early precancerous features
Adenoma-carcinoma sequence
Progression of bowel cancer from normal mucosa to adenoma to cancer
Most non-genetic determined = adenoma
Distribution of adenoma = distribution of bowel cancer
Peak incidence predates cancer
Residual adenoma found in early invasive cancer
Number of polyps
Familial Adenomatous Polyposis
100 polyps minimum to diagnose
Dysplastic polyps = adenomatic
100% risk of development of cancer by 30yo - prophlylactic colectomy around 20yo
FAP genetics
Hereditary autosomal dominant condition
The defective gene is on Chr 5q21 and called APC gene (Adenomatous Polyposis Coli)
Patients acquire the first abnormal gene in utero as germ cell mutation (‘first hit’)
To develop polyps they acquire the second genetic abnormality in the somatic cells (‘second hit’)
Loss of heterozygosity
The loss of the second set of normal genetic material during the ‘second hit’ is termed loss of heterozyosity and cells will acquire two identical copies of abnormal genes i.e. become homozygous for the cancer gene
After the second hit the cells acquire more genetic abnormalities to progress with adenoma-carcinoma sequence
Hereditary non-Polyposis Colorectal Cancer (HNPCC)/Lynch Syndrome
Affecting predominantly the caecum and right colon, before the age of 50
Genetics of HNPCC
Mismatch of base pairs during replicating
G-C -> G-T (no repair genes)
Errors accumulate
Errors in repeat nucleotide
MSH2 (2p16), MLH1 (3p21), PMS 1 and 2
HNPCC Amsterdam Criteria
3+ relatives One should be first degree of other 2 2 or more generations (successive) Before 50yo FAP excluded
Diagnose bowel cancer
History and clinical exam
Anaemia
Flexible sigmoidoscopy and colonoscopy
Bowel cancer symptoms
Change in bowel habit, constipation etc
Bleeding form rectum
Anaemia
Abdominal pain
Duke’s staging
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