Bowel cancer Flashcards
Bowel cancer risk factors (8)
Migration from a low to high risk population.
Foods rick in red meat and fat.
Longstanding UC
Crohn’s disease
Adenoma in colon
Previous bowel cancer surgery
Old age
Family history
Factors that reduce risk of bowel cancer
Food rich in vegetables, fruit and fibres
- Increases faecal bulk
- Reduces transit time so carcinogens spend shorter time in bowel
- Increases short fatty acid chains which increase healthy gut microbes
- Reduces proliferation of potentially neoplastic cells by inhibiting apoptosis
Polyp
- Definition
- Features
Protrusion into a hollow viscus
Can be benign or malignant
Pathological features:
- Hyperplastic: more goblet cells (lace like pattern)
- Tubular adenoma: test tube like
- Villous adenoma
- Tubulovillous adenoma: mixture of tubular and villous
Adenoma
Pre-cancerous lesions
- Dysplastic features
Familial adenomatous polyposis
Presence of at least a hundred polyps in the large bowel.
Polyps are adenomas as they are dysplastic
Increases risk of cancer by 30
Familial adenomatous polyposis genetics
Autosomal dominant inheritance
- APC gene defect
Two hits:
1. Abnormal gene in utero
- Genetic abnormality in somatic cells
Two hit hypothesis
Used to describe how those with FAP develop condition
First hit: Abnormal gene acquired in germ cell
Second hit: Genetic abnormality in somatic cell
Loss of heterozygosity in FAP
When born with one abnormal gene the cells are heterozygous for cancer gene.
When the second hit occurs- loss of heterozygosity as there are now identical copies of the abnormal gene
Progression of normal mucosa to invasive cancer in bowel in FAP.
- 6 steps
- Normal mucosa: first hit
- Inherited or acquired mutation
- Loss of APC gene - Hyperproliferative epithelium
- Methylation abnoralities= 2nd hit - Early adenoma
- K RAS mutation - Intermediate adenoma
- Loss of tumour suppressor genes: SMAD2 - Late adenoma
- Loss of tumour suppressor gene P53 - Invasive cancer
- Telomerase: allows cancerous cell to remain immortal.
Hereditary non-polyposis colerectal cancer (HNPCC)
Lynch syndrome
- Hereditary
- Right colon
Associated with certain cancers:
- Endometrial
- Ovarian
- Small bowel
- UT
2-3% of bowel cancer
Genetics of HNPCC
Mutation in DNA base pair mismatch repair genes
- Mismatched base pairs accumulate
- Expands and contracts tandem repeat nucleotides (microsatellite instability)
4 genese involved:
- MSH2 + MLH1= 30%
- PMS1 + PMS2 = 70%
Two hits are required to develop cancer
- First hit is defective copy of mismatch repair gene
Amsterdam criteria
Guideline for assessing HNPCC. Includes:
- 3 or more relatives with HNPCC associated cancer
with one being first degree relative of the other two.
- Two or more successive generations affects
- Cancer in one or more diagnosed before 30
- Exclusion of FAP as cause
- Tumor must be verified as pathological
Bowel cancer symptoms
Change in bowel habit
- Constipation alternating with diarrhea
Per rectum bleeding
Anaemia
Abdominal pain
Investigations to diagnose bowel cancer
Endoscopy
Flexible sigmoidoscopy and colonoscopy with biopsy
- Biopsy histologically examined
Barium enema (if colonoscopy is not tolerated)
CT/ MRI scan for distal and local metastasis
Duke staging of bowel cancer
Dukes A: 90-95% 5 yr survival
- Cancer in part of the bowel wall
- No lymph node metastasis
Dukes B: 60-70% survival
- Cancer in full thickness of bowel wall
- No LN metastasis
C: 20-25% survival
- Cancer in any part of bowel wall
- LN metastasis
D: <15%
- Liver or other distal metastasis
