Cancer as a Disease – Colorectal Cancer Flashcards
What type of carcinoma are most colon cancers?
Adenocarcinoma
What is the rate of turnover of cells in the colon?
2-5 million cells per minute
- high proliferation rate social ells are vulnerable to mutation
What is a polyp?
Any projection from a mucosal surface into a hollow viscus
What is an adenoma?
Benign neoplasm of the mucosal epithelial cells
What are the different types of colonic polyp?
Metaplastic/hyperplastic Adenoma Juvenile Lipomas Peutz jeghers
State some characteristics of hyperplastic polyps.
These are VERY COMMON
90% of all colonic polyps
They have NO malignant potential
15% have K-ras mutations
What are the different types of colonic adenoma?
Tubular
Tubulovillous
Villous
NOTE: the more villous it is the worse it is
What are the different shapes of colonic adenomas?
Pedunculated – on a stalk- looks like a tree
Sessile – flat and raised looks like a hedge
What is the difference between tubular and villous adenomas?
Tubular– COLUMNAR cells with nuclear enlargement, elongation, multi-layering and loss of polarity + increased proliferative activity + reduced differentiation
Villous– MUCINOUS cells with nuclear enlargement, elongation, multi-layering and loss of polarity. May be exophytic.
What is the most famous condition that causes an increased number of colonic polyps?
Familial Adenomatous Polyposis
What gene mutation is FAP caused by?
5q21
What are the two genetic pathways in colorectal cancer?
- Adenoma-carcinoma sequence = presence of adenomas will increase the risk of colorectal cancer
- Microsatellite instability
What are microsatellites?
Repeat sequences of DNA that are prone to misalignment
Some microsatellites are found in coding sequences of genes which inhibit growth or are involved in apoptosis
State two genetic diseases that predispose to colorectal cancer.
- Familial adenomatous polyposis – inactivation of the APC tumour suppressor gene
- HNPCC – microsatellite instability (affects mismatch repair genes)
State some dietary factors that can increase the risk of colorectal cancer.
High fat
Low fibre
High red meat
Refined carbohydrates
State two dietary deficiencies that can increase the risk ofcolorectal cancer.
- Folates– important for nucleotide synthesis and DNA methylation
- MTHFR (Methylenetetrahydrofolate reductase) – deficiency leads to disruption of DNA synthesis and DNA instability (this leads to mutation). It also causes decreased methionine synthesis leading to genomic hypomethylation and focal hypermethylation – this can have gene activating and silencing effects
What is the clinical presentation of colorectal cancer?
- Change in bowel habit
- PR bleeding
- Unexplained iron deficiency anaemia
Describe the distribution of colorectal cancer.
RECTOSIGMOID –55%
Caecum/Ascending –22%
Transverse –11%
Descending –6%
Describe the Dukes classification of colorectal cancers.
Dukes A
- Growth is limited to the wall (muscularis propria)
- Nodes negative
Dukes B
- Growth beyond the muscularis propria
- Nodes negative
Dukes C1
- Nodes positive
- Apical nodes negative
Dukes C2
- Apical nodes positive
State some clinical features that affect the prognosis of colorectal cancer.
- Bowel obstruction (diminished prognosis)
- Age < 30 (diminished prognosis)
- Distant metastases (diminished prognosis)
State some pathological features that affect the prognosis of colorectal cancer.
- Depth of bowel wall penetration
- Number of regional lymph nodes involved
- Venous invasion
- Lymphatic invasion
What are the criteria for a screening programme?
Condition should be important with respect to the seriousness and/or frequency
The natural history of the disease must be known in order to: Identify where screening can take place
To enable the effects of any intervention to be assessed
What are the characteristics of a screening test?
Simple and acceptable to the patient
Sensitive and selective
Cost effective
Screening population should have equal access to the screening procedure
What does the NHS colorectal cancer screening look for?
Faecal occult blood (FOB)
If positive and 55-60 years = sigmoidoscopy
If positive and over 60-75 years = full colonoscopy
Of cancers how common is colorectal cancer?
4th common cancer worldwide
2nd cause of death in cancers after lung cancer
What does a mutation in APC cause?
cell proliferation
prevents cell loss
What % of adults have adenomas at 50? What % of these becomes cancers if left?
25%
then 5% become cancer if left
What foods can have anti-carcinogenic elements?
- Vitamin C and E- ROS (reactive oxygen species) scavengers
- Isothiocyanates- cruciferous vegetables-auliflower, cabbage, garden cress, bok choy, broccoli, Brussels sprouts and similar green leaf vegetables.
- Polyphenols- green tea and fruit juice
- can activate MAPK pathways regulating phase 2 metabolism to detoxify enzymes
What is the function of the colon?
Extraction of water from faeces
Faecal reservoir
Bacterial digestion for vitamin. production
