Cancers of the GIT

Question 1

what are the hallmarks of cancer?

Answer 1

Evasion of apoptosis
Self sufficiency in growth signals
Insensitivity to anti growth signals
Tissue invasion and metastasis
Limitless replicative potential
Sustained angiogenesis

Question 2

What are the two types of oesophageal cancer?

Answer 2

SCC - Squamous cell carcinoma

ADC - Adenocarcinoma

Question 3

What is the survival chance of oesophageal cancer?

Answer 3

8% 5 year survival

Question 4

What are the risk factors for ADC?

Answer 4

Barrettts metaplasia
about a 0.5% conversion rate from BM to lead to ADC
10% of GORD patients have BM

Question 5

What are the risk factors for Oesophageal adenocarcinoma?

Answer 5

Gender
Age
Reflux
LOS relaxing drugs
Obesity

Helicobacter-pylori (less likely to develop ADC when present)
Fruit and Veg
Anti-oxidants

Question 6

What is an important cause for hypergastrinaemia and duodenal ulcers in the antrum?

Answer 6

Helicobacter Pylori

Prevents the stomach from making acid but causes inflammation leading to the production of gastric ulcers

Question 7

What is a major cause for Gastritis?

Answer 7

Helicobacter pylori

Question 8

How is Hp treated?

Answer 8

Triple therapy consisting of antibiotics amoxicillin and clarithromycin and a proton pump inhibitor

Question 9

How does Hp evolve to colonise the stomach?

Answer 9

Expresses Urease - neutralising gastric acid
Expresses Mucinase - allowing the bacteria to drill into the mucous layer and therefore cause mucosal injury
Expresses Adhesion receptors allowing the bacteria to bind to cells
Expresses exotoxins causing mucosal damage

Question 10

What is the cause of Hereditary diffuse-type gastric carcinoma (HDGC)?

Answer 10

germline mutation in CDH1 gene which encodes for E-cadherin

Question 11

How does a CDH1 mutations lead to cancer?

Answer 11

Abrasion in E-cadherin and therefore leads to cells becoming more motile as they are not adhered to their neighbours. This leads to metastasis and hence can lead to the cells invading new tissues and hence cause cancer.

Question 12

Why is E-cadherin negative more likely to cause cancer?

Answer 12

More likely for cells to become motile and metastasise
Therefore more likely for cells to invade other tissues
Therefore lead to cancers

Question 13

What causes E-cadherin repression?

Answer 13

Epigenetic events
Promoter Hypermethylation (silencing of genes)
EMT regulators

Question 14

What are the main EMT regulators?

Answer 14

Snail and slug

They suppress expression of E-cadherin and instead induce factors associated with mesenchymal transition.

Question 15

What induces snail and slug expression and why is this important?

Answer 15

If we know what induces them then we can prevent their expression leading to EMT and furthermore cancer..

FGF, Wnt, BMP, TGF-beta

Question 16

What are some risk factors associated with colorectal cancer?

Answer 16

Disease of the aged
Meat and fish
Obesity
Lack of physical activity

Question 17

What is the incidence of colorectal cancer?

Answer 17

40,000 per year

Question 18

What is the mortality rate of colorectal cancer?

Answer 18

19,000 per year

Question 19

What is the survival rate of Colorectal cancer?

Answer 19

50%

Question 20

What geographical correlation is related to colorectal cancer?

Answer 20

Associated with western lifestyle

40% of patients may have colorectal cancer prevented if they had adopted a better lifestyle

Question 21

What are the types of colorectal cancer?

Answer 21

Sporadic - 80-90%

Familial - 10%

Question 22

What are the 2 main types of Familial colorectal cancer?

Answer 22

FAP - Familial adenomatous polyposis

HNPCC (leech syndrome) -

Question 23

What is a treatment for FAP?

Answer 23

Colectomy

Question 24

What is the tumour suppressor for FAP?

Answer 24

ACP - adenomatous polyposis coli

Question 25

How does APC work?

Answer 25

When the APC is lost it leads to FAP.

Beta catenin can enter cells and induce oncogenes

APC is involved in the mechanism in regulation of Beta catenin.
GSK-3beta phosphorylates Beta catenin leading to its degradation.

Question 26

Why does a patient with a mutation in APC lead to FAP?

Answer 26

Mutant APC cannot be phosphorylate and degrade Beta-catenin and therefore it is able to enter the nucleus and induce oncogenes leading to cancer.

Question 27

How do sporadic colorectal cancers develop?

Answer 27

Through Adenoma carcinoma sequences

Question 28

How does the adenoma carcinoma sequence lead to cancer?

Answer 28

APC is randomly mutated and this may lead to genomic instability and thus more alterations in other alleles can be caused and hence lead to metastasis and cancers.

Question 29

How is the 5 year survival rate of colorectal cancer being improved?

Answer 29

By the development of an Asymptomatic screening program.

Looking for diseased individuals without symptoms and therefore find disease early and hence should be more curable.

Question 30

How does the screening program work?

Answer 30

Over the ages of 60 are sent a stool smear test kit and where they send off stool to be examined for blood to see if they have disease.

Question 31

What is a surveillance program?

Answer 31

Where disease has been Identified and the patients are now being monitored for other disease.

Question 32

What is personalised medicine?

Answer 32

Tailored treatment of a disease to an individual to ensure that the persons treatment is responsive.

Question 33

How is personalised medicine being produced?

Answer 33

Tumours removed are genomically sequenced to therefore be tested to see which drugs they respond to and hence are able to therefore tailor new medicines to people with similar genomical tumours.