Aetiology Flashcards
Outline the pathway of CRC development
- Normal epithelium
- APC gene inactivation
- Early adenoma
- Further mutations in other tumour suppressor genes (e.g. KRAS and p53) lead to late adenoma and eventually…
- Carcinoma
THM: the accumulation of many mutations
List 5 risk factors for CRC
- Red and processed meat intake
- Smoking
- Genetic syndromeS (Lynch syndrome, FAP)
- FHx of CRC
- Smoking
- IBD (e.g. Crohn’s, UC)
- Obesity
- Low-fibre diet
- Alcohol
The classic adenoma-carcinoma sequence accounts for up to 80% of sporadic colon tumors and typically includes mutation of ___ early in the neoplastic process
The classic adenoma-carcinoma sequence accounts for up to 80% of sporadic colon tumors and typically includes mutation of APC early in the neoplastic process
In patients with DNA mismatch repair deficiency, mutations accumulate in _______ repeats, a condition referred to as ___________ __________.
In patients with DNA mismatch repair deficiency, mutations accumulate in microsatellite repeats, a condition referred to as microsatellite instability (MSI).
What is the function of the APC gene?
It is a member of the class of tumour suppressor which function by downregulating growth-promoting signalling pathways.
What happens when APC is mutated?
When APC is mutated or absent, as frequently occurs in colonic polyps and cancers, the destruction of β-catenin cannot occur.
β-catenin translocates to the nucleus and coactivates genes that promote entry into the cell cycle, and cells behave as if they are under constant stimulation by the WNT pathway.
(Robbins pg. 297)
What is the action of p53?
TP53: Guardian of the Genome.
TP53, a tumor suppressor gene that regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis, is the most frequently mutated gene in human cancers.
What is the WNT signaling pathway?
A group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors.
