Week 8 Colon Cancer Flashcards
Colon cancer or Colorectal cancer (CRC) is a disease of what organ?
Cancer of the Large bowel (and rectum).
What interventional imaging methods can be used to view CRC?
Colonoscopy or Sigmoidoscopy
Mutation of what particular gene are present in most sporadic CRC tumours and inherited bowel cancer syndromes?
APC (Adenomatous Polyposis Coli) protein
Why is the Colon a good predisposing origin for cancer to strike?
The cells of the bowel sit very close in contact with eachother, and there is a high cell turnover.
APC is a multifunctional protein, name some of the roles of APC:
Promotes cell migration
Regulates Migrotubule function (cell division)
Promotes cell maturation/differentiation (through B-catenin regulation)
Obviously APC mutations will act to inhibit any/all of the above
HNPCC involves changes in MMR - what are these abbreviations?
Hereditary Non-Polyposis Colon Cancer
Mismatch Repair
APC has huge domains and cellular functions in the maturation of cells - what particular dual function protein does it regulate?
B-catenin
APC is it a oncogene or tumour suppresor gene?
Tumour suppressor gene
If there is a mutation in the APC gene (usually frameshift) what inherited condition thats is a predisposition to cancer can arise - and what is the phenotype?
FAP - familial adenomatous polyposis
and the phenotype is polyps which increases the risk of cancer
CRC is the ….. most common cancer in the world
3rd
what are the 4 most common cancers worldwide?
Breast,
Lung,
CRC,
and Prostate
Comparing with incidence CRC is third most common cancer in the world, but where does it rank in terms of most common death?
2nd in the world, with Lung cancer way ahead - because of lack of effective therapies.
Name the parts of the Large colon (left to right).
(appendix) Caecum, Asc Colon, Transverse Colon, desc Colon, Sigmoid Colon and Rectum
What side do the majority of cancer arise in the large colon?
the L.H.S (patients left)
Name some risks for increase in CRC:
Age,
Weight (obesity)
Increase Alcohol intake
Smoking
Diet
High fat, increase red meat, processed meats
Genetics (FAP (1%) - lots of polyps increased risk of benign to malignant, HNPCC (Lynch Syndrome)
Inflammation
Crohns disease, U.Colitis
Why are processed meats thought to increase the risk of CRC?
Because of the additives and preservatives within them, that keep the meat for longer. Haem and Iron alterations.. and free-radicals
What diet and lifestyle would decrease your risk of CRC?
Low fat, low intake red meat/processed, high fibre, vegtarian, non-smoker, exercise
Why does inflammation play a key role in Cancer? - Discuss with group
- A lot to mention here
NSAIDs help in treating conditions of Inflammation, what is the name of the trial that looks to add NSAIDs into CRC patient regimes.
ADD-Aspirin trial (UCL)
Why would some places such as India have a decrease in CRC than places such as New zealand or North America?
because of being a less economically developed country, there amy be less carcinogens, diet containing less red meat, less processed food, obesity is less
FAP is characterised by what phenotypically?
multiple polyps, like multiple benign lesions that are predisposition for cancer
name some symptoms of bowel cancer
abdominal pain blood in stool weight loss diarrhoea bloated feeling loss of hunger mucus altered bowel habits
A physician on palpating would find some organomegaly of the large intestine in the lower abdomen. They would find a palpable lump.
what surgical imaging would they use to observe? (intervention)
(flex) sigmoidoscopy or colonoscopy - these would also be fitted with pincers if wanting to do a biopsy
what type of enema would you use to observe the colorectal cancer
Barium salt enema, which would allow xray of the bowel to see the shape.
What further diagnostic imaging would be used to see in detail about cancer progression?
CT scan
Name the standard of care Chemotherapies normally given for CRC
5FU, folinic acid and Oxaliplatin (FOLFOX)
5FU, folinic acid and Irinotecan (FOLFIRI)
surgery and chemotherapy if needed..
for those not tolereant with the above.. Capecitabine given.
Colonscopy observes what part of the colon?
observes all of the length of the colon
barium enema can be used for what other conditions other than CRC?
UC, Crohns, IBD, Polyps etc
what is the name of the screening kit in the pilot study for CRC in the midlands? what does it do and what are the problems..
Faecal Occult stool test
It tests to see if there is any blood in the stool, but the problem is that these reading may be false positives.. almost 90% of these colonoscopies offered are negative if positive in the test - therefore cost a lot of money and a lot of time. selectivity - tricky.
Explain the staging in CRC
1 - confied to inner mucosa
2 - grown into the muscle wall
3 - spread to at least one lymph node
4 - spread to distant sites (metastasis)
the 5 year survival rates are lower as the stages progress
Biology of Cancer (Garland science 2007) use this reference if you do essay on this question.
.
The villi, contain cells that proliferaton and differentiate upwards. What is the bottom of the villi called?
Crypts
Where are the stem cells located in the villi?
in the crypts
What does Wnt bind to to consequentally promote proliferation in CRC cells?
Wnt binds to Frizzled
How does a oncogene form?
When there is a mutation in a proto-oncogene that mediates a change for it to become a oncogene.
APC is mutated in around what percentage of CRC cancers?
80%
In a normal cell the main purpose is to phosphorylate B-catenin, which then leads to degradation of itself to the proteosome. What happens in Mutated APC?
Wnt binds to Frizzled which activates Dishevelled there is the Axin, APC, GSK-3beta complex.. but because there is a mutation in aPC.. GSK-3beta is inactive and the Beta-catenin that woudl usually bind here does not and they goes on downstream to promote cell proliferation
As aforementioned APC is a Tumour suppressor gene. And if mutated this can lead to the future polyp formation. What other way can this be caused in the pathway?
If Beta catenin is mutated
what does CIN stand for in terms of a solid tumour growth?
carcinoma in situ
As mentioned before 80% of sporadic CRC have lost APC function. Decribe what the The Vogelgram is?
Created by bert Vogelstein - it maps the changes in proto-oncogenes (to oncogenes) and TS genes.
APC is usually the earliest in terms of loss of function, this causes normal epthelium to become hyperplastic.. and then other DNA epitope modifications such as DNA hypomethylation can occur.. leading to progressive Adenomas. In addition to this hyper-activation of K-Ras (Ras related proteins) from a mutation and loss of other TSGs along the way can lead to the formation of a carcioma.. which consequently will cause a progressive cancer. It essentially highlights the checkpoints, similar to a having multiple hits forming a cancer. The loss of p53 in the TSG stage is particularly important as it confers the change from benign to malignancy.
it is important to understand that not all cancers follow this simple route of loss of gene function.. oncogene formations.. TSG loss. THERE ARE SO MANY FACTORS IN EARLY TO LATE STAGE CANCER - THINK OF THE HALLMARKS!
.
name some effects of APC truncation
slower cell migration, therefore they are exposed to carcinogens more than unmutated cells in the lumen.
beta catenin misregulation
altered microtubules,
poor cell division
chromosomal instability
aneuploidy of CRC cells
Name two techinique that can be used in future for screening for CRC
Digital PCR
BEAMing
these will look for APC mutations
