13. Colorectal cancer Flashcards
(34 cards)
What is the function of the colon?
- Extracts water from faeces (slightly involved in electrolyte balance)
- Faecal reservoir
- Bacterial digestion of vitamins
How fast do the bowel cells turnover and what eliminates genetically defective cells?
- 2-5 million cells die per minute
- Proliferation renders cells very vulnerable
Protective mechanisms to eliminate cells:
• Natural loss
• DNA monitors e.g. APC (adenomatous polyposis coli)
• Repair enzymes
What is a polyp?
- Any projection from a mucosal surface into a hollow viscus
* May be hyperplastic, neoplastic, inflammatory etc.
What is an adenoma?
Benign neoplasm of the mucosal epithelial cells
What are the colonic polyp types?
- Meta/hyperplastic - benign and common (mucosal damage)
- Adenomas - increase RISK of cancer
- Juvenile
- Peutz Jeghers
- Lipomas
- Others
Outline hyperplastic polyps?
- Very common and benign
- Not dysplastic
- 90% of all LI polyps
- No malignant potential
- 15% have k-ras mutation
What are the colonic adenoma types?
- Tubular - look like test tubes lined up (most common)
- Villous - look like sea anemone
- Tubulovillous - mixture of both
- Pedunculated - like a tree
- Sessile - like a rug on top of a carpet
Describe tubular adenomas
- Columnar cells with some elongation, nuclear enlargement, multi-layering and loss of polarity
- Increased proliferative activity
- Reduced differentiation
- Disorganised
- Hyperchromatic - look darker on slides (increased nucleus:cytoplasm)
Describe villous adenomas
- Mucinous cells with elongation, nuclear enlargement, multi-layering and loss of polarity
- Exophytic, frond-like extensions
- Rarely may have hyper-secretory function and result in excess mucus discharge and hypokalaemia
What is dysplasia?
- Abnormal growth of cells with some features of cancer
- Not yet cancer
- Disorganised
- Pseudostratification and granular hyper-chromatic dark nuclei
- Increased nucleo-cytoplasmic ratio
What is familial adenomatous polyposis?
- Disease in which there are thousands of polyps in the bowel
- Cancer is inevitable - prophylactic colectomy can stop this
- Mutation in 5q21 gene
- Associated with APC gene
- Site of mutation determines clinical variants
Does the size of a polyp change the risk of cancer?
Yes, large polyps have a higher risk of cancer
What is the incidence of cancer if a polyp is left?
5%
Mutations in what genes can increase the risk of getting polyps => adenoma carcinoma?
- APC
- k-RAS
- Smads
- p53
- Telomerase activation
What are microsatellites, what is microsatellite instability and how is this involved in adenoma carcinomas?
- Repeat sequences prone to misalignment
- Some microsatellites are in coding sequences of genes which inhibit growth or apoptosis
- Microsatellite instability results from impaired “mismatch repair genes”
- DNA can’t be repaired
- DNA damage accumulates and leads to cancer
- Recessive gene requiring 2 hits
- HNPCC - germ-line mutation in these genes
What 2 main genes pre-dispose someone to an adenoma carcinoma?
- FAP - inactivation of APC tumour suppressor genes
* HNPCC - microsatellite instability
When does an adenoma become a carcinoma?
When it invades the adjacent tissue
Can cooking food be dangerous?
- Yes, damaging and destroying it can release materials that may be carcinogenic
- Includes heterocyclic amines
What deficiencies are linked with colorectal cancer?
- Folate - it is a protector of cells and destroyed by over-cooking
- It is also a co-enzyme for nucleotide synthesis and DNA methylation
- MTHFR mutation affects the body’s ability to use folic acid -
- Decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation
List some anti-cancer food elements
- Vitamin C - ROS (reactive oxygen species) scavenger
- Vitamin E - ROS scavenger
- Isothiocyanates (cruciferous vegetables)
- Polyphenols - green tea (activate MAPK, EGCG-induced telomerase activity)
- Garlic - associated with apoptosis
Outline the clinical presentation of colorectal cancer
• Change in bowel habit
• Rectal bleeding
• Unexplained iron deficiency anaemia
(mucus, bloating, cramps, weight loss, fatigue etc.)
Why do people not present very often thinking they have colorectal cancer?
- People ignore the symptomatic presentation
* Patient’s (and doctors) rationalise these symptoms as ‘getting old’ etc.
Describe the distribution of colorectal cancer in the bowel?
- Caecum/ascending colon - 22%
- Transvers colon - 11%
- Descending colon - 6%
- Recto-sigmoid - 55%
Very similar to adenomas
What type are almost all cancers of the large bowel?
Adenocarcinomas (malignant tumours of glandular epithelium)
