Bowel Cancer Flashcards
Prevalence
3rd most common cancer in women and men
High incidence in Western world, low incidence in Asia and Central Africa
Affects men and women equally
Risk Factors
Moving from low risk to high risk area Foods rich in red meat Vegetables fruit and fibre = lower risk due to increased faecal bulk and reduced transit time Physical activity and low BMI = low risk Longstanding UC Crohn's disease Presence of adenoma in large bowel Previous family history or history of bowel cancer surgery Old age
How does fibre reduce risk
Increases formation of short chain fatty acids, promoting healthy gut micro-organisms and reduces proliferation of potentially neoplastic cells
Reduced transit time - potential carcinogens have a shorter contact with bowel mucosa
Reduces formation of secondary bile acids (potentially carcinogenic)
Definitions
Polyp: protruding growth into a hollow viscous - benign, adenoma, malignant
Don’t use term polyp if cancer is polypoid
Most polyps in LI are adenomas and consist of dysplastic epithelium
Dysplasia: the cells have morphological features of cancer but without invasion of the surrounding tissue
Low grade dysplasia: early precancerous features
High grade dysplasia: advanced precancerous features - high risk of invasion
Diagnosis only confirmed on microscopic examination by pathologist
Features of polyps
hyperplastic (benign) consists of numerous goblet cells when compared to normal mucosa; has a lace-like pattern
Tubular adenoma has test-tube like appearance
Villous adenoma has a finger-like appearance
Tubulovillous adenoma has a mixture
Adenoma-carcinoma sequence
Populations with a high prevalence of adenomas have a high prevalence of cancer
Distribution of adenomas mirrors that of bowel cancer - 60% of both raisin left colon and rectum
Peak incidence of polyps predates development of cancer - peak age differs by about 11 years
Residual adenoma is found in most cases of early invasive cancer
Risk of cancer is directly related to the number of polyps
Programmes which follow-up patients and remove adenomas reduce the incidence of bowel cancer
Familial Adenomatous Polyposis (FAP)
Patients with FAP have hundreds to thousands of polyps in large bowel, 500 – 2500
A minimum of 100 polyps is required to make diagnosis FAP
The polyps are dysplastic and therefore called adenomas
FAP is associated with 100% risk of development of cancer by age of 30
Patients undergo prophylactic colectomy around the age of 20
FAP contributes to 1% of bowel cancer
Genetics of FAP in bowel cancer
Hereditary autosomal dominant condition
The defective gene is on Chr 5q21 known as the APC gene (Adenomatous Polyposis Coli)
Patients acquire the first abnormal gene in utero as a germ cell mutation known as the ‘first hit’
To develop polyps they acquire the second genetic abnormality in the somatic cells known as the ‘second hit’
The ‘second hit’ paves the way for the development of polyps from a young age throughout the teens
Patients have no polyps at birth and require ‘the second hit’ to develop polyps
Two hit hypothesis
In FAP first hit = genetic abnormality, second hit = after birth
In sporadic bowel cancer the person requires 2 hits in somatic cells to develop adenomas
Hypothesis proposed by Knudson
2nd hit leads to loss of heterozygosity - cells will acquire 2 identical copies of abnormal genes
Genetic abnormalities associated with bowel cancer
Lynch Syndrome (previously Hereditary Non-polyposis Colorectal Cancer (HNPCC)
Familial adenomatous polyposis (FAP)
Attenuated FAP - less than 100 adenomas
Familial Colorectal Cancer Type X (FCCX)
MUTYH Associated Polyposis (MAP)
Serrated Polyposis Syndrome
Hamartomatous Polyposis Syndrome
Lynch Syndrome
Affects predominantly caecum ad right colon, before age 50
Associated with endometrial, small bowel and cancer of the urinary tract
Familial cancer
LS accounts for 2-3% of bowel cancer
No precursor polyps
Bowel cancer from young patients tested routinely for LS genetic mutations
Genetics of Lynch Syndrome
During replication the DNA base pairs can mismatch e.g. Guanine – Thymine instead of Guanine – Cytosine
Mismatch repair genes correct these (without them errors would accumulate creating microsatellites - tandem repeats of nucleotides)
Errors due to mismatch lead to instability of microsatellites
4 mismatch repair genes involved in LS - tested for
MSH2 (2p16) and MLH1 (3p21) genes account for 30%;
PMS1 and PMS2 also involved
Same first and second hit theory
LS assessed using Amsterdam Criteria
Three or more relatives with LS-associated cancer (bowel cancer or cancer of the endometrium, small bowel, ureter or renal pelvis) plus all of the following:
One affected patient should be a first-degree relative of the other two;
Two or more successive generations should be affected;
Cancer in one or more affected relatives should be diagnosed before the age of 50 years;
Familial adenomatous polyposis should be excluded in any cases of colorectal cancer;
Tumours verified by pathological examination
Symptoms of Bowel Cancer
Asymptomatic and detected during screening
Change in bowel habit: constipation alternating with diarrhoea due to an obstructive cancer
Bleeding from rectum
Anaemia – especially with cancers of the caecum
Abdominal pain due to obstruction
Diagnosis and Staging
History and clinical examination
Flexible sigmoidoscopy and colonoscopy with biopsy and histological exam
CT colonography for patients who cannot tolerate colonoscopy
Staging CT scan for distal metastasis
MRI for rectal cancer to assess local spread
T = Tumour; assesses depth of invasion of the bowel wall
N = Lymph node metastasis
M = Distant metastasis to liver of lung
Bowel wall consists of mucosa to the end of external muscularis propria
