MOD Neoplasia III

Question 1

Give 3 intrinsic factors in neoplasia pathogenesis

Answer 1

Heredity
Age
Gender

Question 2

Give 3 extrinsic factors in neoplasia pthogenesis

Answer 2

Environment

Behaviour

Question 3

Give 5 behavioural risk factors. Proportion of cancer death?

Answer 3

Smoking
Alcohol
High BMI
Low fruit/veg
Lack of exercise
30%

Question 4

Give 3 extrinsic carcinogens. Proportion of cancer risk?

Answer 4

Chemical
Infection
Radiation
85%

Question 5

Give three factors of chemical carcinogens causing cancer, with example.

Answer 5

Long delay between exposure and malignant neoplasm formation.
Dose dependent, greater dose, more neoplasm.
Can be organ specific.
E.g. 2-naphthalamine causes bladder cancer.

Question 6

Give 3 chemical carcinogens

Answer 6

Polycyclic aromatic hydrocarbons
-lung, bladder, skin
Aromatic amines
-bladder cancer.
Alkylation agents

Question 7

What are initiators?

Answer 7

Mutagenic agents that cause carcinogenic mutation in either TSGs or proto-oncogenes.

Question 8

What are promoters? Give examples

Answer 8

Induce tumours in initiated cells by promoting proliferation and increasing incidence of further mutation.
E.g. Hormones, local tissue responses, growth factors

Question 9

What are pro carcinogens?

Answer 9

Metabolised in the liver by the cytochrome P450 system to a carcinogenic agent.

Question 10

What is a complete carcinogen?

Answer 10

Acts as both intiator and promoter

Question 11

Describe how radiation causes mutation.

Answer 11

Direct DNA damage

• altered bases
• double stranded breaks

Indirect DNA damage
- free radicals

Question 12

Describe nucleotide excision repair and base excision repair

Answer 12

Damaged DNA excised and replaced by DNA polymerase.
Nucleotide - 30 bases due to Uv damage
Base - 1-5 bases due to oxidative damage

Question 13

Describe the different exposures to types of radiation

Answer 13

UV radiation form sunlight
Ionising radiation from radon, medical tests
Nuclear radiation
Alpha, beta, gamma

Question 14

How does HPV cause cancer? Which?

Answer 14

HPV expresses two proteins E6/E7 that inactivate TSG proteins p53 and pRb.
This results in cell speeding through cycle by activating cyclins and CDK with no restriction checking, and apoptosis inhibition.
Activate telomerase.
Cervical carcinoma

Question 15

How can causes of neoplasia be divided?

Answer 15

Intrinsic and extrinsic factors

Question 16

How do Hep B and C cause cancer?

Answer 16

Indirect carcinogens
Cause chronic hepatocyte injury.
This leads to increased cell division, which results in increased mutation risk.
Hepatocellular carcinoma

Question 17

How does helicobacter pylori cause cancer

Answer 17

Indirect
Chronic gastric inflammation
Increased risk of gastric carcinoma

Question 18

How does Epstein Barr cause cancer?

Answer 18

Viral genes disrupt normal proliferation.
Increased acquired mutation risk
Hodgkin’s lymphoma

Question 19

How does HIV lead to cancer

Answer 19

Reduced immunity

More mutagenic infections

Question 20

How do parasitic flukes cause cancer

Answer 20

Inflammation of bile ducts/bladder
Increased regeneration
Increased mutation risk
Cholangiocarcinoma
Bladder carcinoma

Question 21

Describe the 2 hit hypothesis using Retinoblastoma example

Answer 21

In familial retinoblastoma, one hit is inherited in the germ line. Thus only one hit must be acquired in the TSG for inactivation.
In sporadic retinoblastoma, no hit is inherited so both hits must be acquired.
A hit is a procarcinogenic mutation

Question 22

Give the difference in mutations required for neoplasm in TSGs and Protooncogenes

Answer 22

TSG
Both alleles must be mutated to inactivate the TSG which acts as breaks on the cell cycle to suppress growth
protoongenes
Normal gene that becomes oncogene by one mutation resulting in activation enhancing neoplastic growth.

Question 23

What is RAS

Answer 23

Proto oncogene that encodes a small G protein that pushes cell past the restriction point in the cell cycle.
Mutant RAS is always active, constantly producing a signal to pass the restriction point

Question 24

What is RB

Answer 24

A TSG that inhibits cell proliferation by inhibiting passage through restriction point.
Inactivation of both RB alleles allows unrestrained passage rough cell cycle.

Question 25

What is p53

Answer 25

TSG that encodes a protein important for expression of cell cycle arrest, DNA repair and apoptosis genes

Question 26

What happens in xeroderma pigementosa

Answer 26

Mutations in DNA excision repair genes
Very sensitive to UV damage
Skin cancer at young age
More mutation

Question 27

What occurs in hereditary non polyps is colon cancer syndrome

Answer 27

Mutation in DNA mismatch repair genes.
Microsattelite instability
More mutation

Question 28

What occurs in familial breast cancer

Answer 28

BRCA1 and BRCA2 important for repairing double strand DNA breaks
Leads to chromosomal instability
More mutation

Question 29

What is genetic instability

Answer 29

Accelerated mutation rate in malignant neoplasm

Question 30

What are caretaker genes

Answer 30

Genes TSG that maintain genetic stability

Question 31

6 hallmarks of cancer

Answer 31

Self sufficient growth signals
Resistance to stop growth
No limit on cell decision, telomerase
Angiogenesis inducing
Resistance to apoptosis
Invade and metastasise

Question 32

What is the angling characteristic

Answer 32

Genetic instability

Question 33

Colonic Adenoma carcinoma sequence - describe progression.

Answer 33

Cancers require acquired mutations in multiple TSGs and proto-oncogenes.
Early adenomas, later adenomas, primary carcinomas and metastatic carcinomas show that stepwise accumulation of mutations occurs throughout this sequence over time.
Approximately 10 required
Stepwise accumulation of mutations is progression