Colorectal cancer Flashcards
What types of colorectal neoplasia exist?
Benign: adenoma
Malignant: adenocarcinoma
What types of colorectal polyps exist?
Inflammatory
Hamartomatous (occur as a result of faulty development)
Metaplastic
Neoplastic (i.e. adenoma)
what do oncogenes do
a) when normal
b) when mutated
a) promote cell growth and division
b) When mutated cause excess cell growth and division (gain of function)
What do tumour suppressor genes do
a) when normal
b) when mutated?
a) suppress cell growth and division
b) allow cell growth and division (loss of function)
What are the genetic/epigenetic abnormalities involved in the adenoma-carcinoma sequence of colorectal cancer?
Activation of oncogenes
Loss or mutation of tumour suppression genes
Defective genes of the DNA repair pathway leading to genomic instability
Which oncogenes are most frequently altered in colorectal cancer?
What do these alterations cause to occur?
KRAS
c-MYC
Point mutations in KRAS:
Can lead to EGFR (epidermal growth factor receptor) independent activation of the MAPK (mitogen-activated protein kinases) pathway inducing cell proliferation, preventing apoptosis, and promoting invasion, metastasis and neovascularisation.
Overexpression of c-MYC:
a feature of most colorectal cancers
it encodes a nuclear phosphoprotein that is required for DNA synthesis
increased expression may be followed by increased cellular proliferation
What may contribute oncogene activation?
Age related hypomethylation
Which tumour suppression genes are altered in colorectal cancer?
Point mutations in APC (adenomatous polyposis coli) gene MCC (mutated in colorectal cancer) DCC (deleted in colorectal cancer) TP53 (gene product is p53) Deletions in NME1
What alteration occurs in the APC gene, and what is the effect?
Point mutations.
Subsequent deletion of the accompanying normal allele results in the complete loss of the tumour suppressor function, leading to colorectal cancer.
What alteration occurs in the MCC gene and what is its effect?
MCC- mutated in colorectal cancer
The gene product is involved in cell cycle control
What alteration occurs in the DCC gene and what is its effect?
DCC- deleted in colorectal cancer
Involved in the control of apoptosis
What is the product of the TP53 gene and what does it do?
The product is p53.
This is a nuclear protein that can hold the cell cycle at the G1/S checkpoint and allow time for succesful DNA repair, or initiate apoptosis if the DNA damage is irrepairable.
What alteration may occur to the NME1 gene and what is the result?
Deletions
May facilitate metastasis
What factors contribute to the development of colorectal cancer?
Inherited genetic factors
Long-standing ulcerative colitis
Environmental factors:
Mostly dietary, e.g. high fibre diet is protective
Where do colorectal cancers occur?
Why is this of clinical importance?
50% in the rectum
30% in the sigmoid colon
The rest are equally distributed in the caecum, ascending, transverse and descending colon
This is important because about 50% of colorectal cancers can be reached with a finger and 80% with the sigmoidoscope.
What are the different types of macroscopic appearances of colorectal cancer?
Ulcerative
Polypoidal
Annular/stenosing
What type of cancers are the majority of the ones in the rectum?
How do they present?
Ulcerative.
They usually present with rectal bleeding.
Where are annular/stenosing type cancers mostly seen?
What do they cause?
The descending colon and sigmoid.
They usually precede obstruction relatively early because of the narrowing of the lumen and the solid consistency of the faeces at this site.
Where are polypoid cancers more common?
What do they cause?
The right colon
They tend to cause recurrent occult bleeding and the patient develops iron-deficiency anaemia. These tumours are more likely to be advanced at the time of presentation.
