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
What is a polyp?
Any projection from a mucosal surface into a hollow viscus, may be hyperplastic, neoplastic, inflammatory
What is an adenoma?
Benign neoplasm of the mucosal epithelial cells
List 3 different types of colonic polyp
Metaplastic/hyperplastic
Adenoma
Lipoma
State 4 characteristics of hyperplastic polyps.
VERY COMMON (90% of all colonic polyps)
< 0.5cm
NO malignant potential
15% have K-ras mutations
What are the different types of colonic adenoma?
Tubular (majority)
Tubulovillous
Villous
The more villous it is the worse it is
What are the different shapes of colonic adenomas?
Pedunculated: looks like a tree (more successful removal)
Sessile: looks like a hedge
What is the difference between tubular and villous adenomas?
Tubular: COLUMNAR cells with nuclear enlargement, elongation, multi-layering, loss of polarity, increased proliferative activity, reduced differentiation + disorganisation of architecture
Villous: MUCINOUS cells with nuclear enlargement, elongation, multi-layering + loss of polarity. May be exophytic. May have hypersecretory function leading to hypokalaemia.
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 (origin of most CRCs)
Microsatellite instability
What are microsatellites?
Repeat sequences of DNA prone to misalignment
Some are found in coding sequences of genes which inhibit growth or are involved in apoptosis
If mismatch repair genes mutate, results in microsatellite instability, leads to CRC
State two genetic diseases that predispose to colorectal cancer.
Familial adenomatous polyposis: inactivation of APC tumour suppressor gene
HNPCC: microsatellite instability (affects mismatch repair genes)
State 4 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: co-enzyme for nucleotide synthesis + DNA methylation
MTHFR: disruption of DNA synthesis + DNA instability (leads to mutation). Decreases methionine synthesis leading to genomic hypomethylation + focal hypermethylation (gene activating + silencing effects)
What is the clinical presentation of colorectal cancer? (7)
Change in bowel habit PR bleeding Unexplained iron deficiency anaemia PR mucus Bloating Cramps/ Colic Weight loss/ fatigue
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 limited to the wall (mucosa + submucosa) Nodes negative Dukes B Growth beyond muscularis propria Nodes negative Dukes C1 Nodes positive Apical nodes negative Dukes C2 Apical nodes positive
State 3 clinical features that diminish the prognosis of colorectal cancer.
Bowel obstruction/ perforation
Age < 30
Distant metastases
State 5 pathological features that affect the prognosis of colorectal cancer.
Degree of differentiation 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 +/or frequency
Natural history of the disease must be known in order to: Identify where screening can take place
To enable effects of any intervention to be assessed
What are 4 characteristics of a screening test?
Simple + acceptable to patient
Sensitive + 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 + 55-60 years = sigmoidoscopy
If positive + >60 years = full colonoscopy
State the 6 layers of the colonic wall
Mucosa: Epithelium + Lamina propria Muscularis mucosa Submucosa Muscularis propria Serosa Mesenteric fat
What characteristic of cell lifespan in the colon renders it vulnerable to mutation? What natural mechanisms do we have to eliminate mutated cells?
High cell turnover- more likely mutation will occur
Natural loss (sloughed off at top of villus)
DNA monitors
Repair enzymes
What is the function of APC? Why does dysfunctional APC cause cancer?
APC holds B catenin in inactive state in cytoplasm
Mutated APC doesn’t bind B catenin, so B catenin moves into nucleus, increases cell proliferation
How does colorectal cancer incidence change with age?
Increases with age
What pathological feature can improve prognosis of colorectal cancer?
Local inflammation + immunologic reaction
What features indicate high risk for colonic cancer?
Previous adenoma
1st degree relative affected by CRC <45
IBD
Hereditable cancer families
