Gastrointestinal Cancers

Question 1

What are the 6 hallamarks of cancer?

Answer 1

1. evasion of apoptosis
2. self sufficiency in growth signals
3. insensitivity to anti-growth signals
4. tissue invasion and metastasis
5. limitless replicative potential
6. sustained angiogenesis

Question 2

What are the two types of oesophageal cancer?

Answer 2

adenocarcinoma - GORD –> barrets metaplasia –> dysplasia –> cancer

squamous cell carcinoma

Question 3

What happens in Barret’s metaplasia?

Answer 3

Stratified squamous epithelium becomes replaced by simple coulumnar epithelium

Question 4

What is the aetiology of oesophageal adenocarcinoma? What are the risk factors?

Answer 4

• gender
• age
• reflux
• LOS relaxing
• drugs
• obesity
• H-pylori
• fruit and vegetables
• anti-oxidants

Question 5

What is the most important risk factor for gastric cancers?

Answer 5

helicobacter pylori

Question 6

What does H.Pylori do in the antrum vs corpus? What is the treatment?

Answer 6

Antrum - hypergastrinaemia and duodenal ulcers ( G cells hypersecrete gastrin, decreased antral D cell somatostatin release, both leads to increase in acid secretion)

Corpus - hypochlorhydria and gastric ulcers ( Hp leads to an inflammatory response which induces interleukin 1 beta (IL1B) which down regulates gastrin and induces somatostatin -> suprreses parietal cell acid secretion)

Triple therapy - amoxicillin, clarithromycin, PPI

Question 7

What is the cause of hereditary diffuse gastric cancer?

Answer 7

Caused by germline mutation in CDH1 gene. This is a mutation in E-cadherin which normally acts as a zip holding cells together. A mutation means that cells o longer adhere to each other and become very motile. Cells detach from primary tumour and metastasize.

Question 8

What causes E-cadherin repression?

Answer 8

Epigenetic events such as promoter gene hypermethylation.

EMT regulators- proteins that induce epithelial mesenchymal markers and suppress E cadherin expression.

Question 9

What are the risk factors for colorectal cancer?

Answer 9

• high iron - meat and fish
• low fibre
• obesity
• alchohol
• low physical activity

Question 10

What are the 2 types of colorectal cancer?

Answer 10

sporadic (80-90%)- random events that occured over many years, mainly elderly

familial e.g Familial adenomatous polyposis coli (FAP) and HNPCC- germline mutation, usually young patients

Question 11

What is FAP

Answer 11

Familial adenomatous polyposis coli

• multiple benign aenomatous polyps at an early age
• mutated APC gene- (tumour suppressent gene) on chromosome 5q21
• treated y prophylactic colectomy

Question 12

What happens to colon cancer cells in FAP?

Answer 12

• APC, Axin and GSK3ß are proteins that normally bind to ß-catenin and regulate ß-catenin via the Wnt pathway
• In cancer cells, APC becomes mutated, this causes ß-catenin to be accumulated in the cytoplasm. ß-catenin enters the nucleus and bind to transcription factors. This leads to uncontrolled cell growth