Neoplasia 3

Question 0

Give some intrinsic factors for the cause of cancer

Answer 0

Heredity
Age
Gender
Chronic inflammation

Question 1

Define carcinogenesis

Answer 1

Cause of cancer

Question 2

Give some extrinsic factors for cancer risk

Answer 2

Smoking
Alcohol
Lack of exercise
Chemicals
Infection
Radiation
Diet
-high BMI
-low fruit and veg

Question 3

What do initiators and promoters do?

Answer 3

Initiators are mutagens

Promoters cause prolonged proliferation in target tissue

Question 4

What are pro-carcinogens?

Answer 4

Chemicals that are only converted to carcinogens by the cytochrome P450 enzymes in the liver

Question 5

What are complete carcinogens?

Answer 5

Carcinogens that act as both initiators and promoters

Question 6

What does ionising radiation do to DNA?

Answer 6

Damages DNA bases

Causes single and double strand DNA breaks

Question 7

How do infections cause cancer?

Answer 7

Affect genes that control cell growth
Cause chronic tissue injury where the resulting regeneration either acts as a promoter for any pre-existing mutations of causes new mutations from DNA replication errors

Question 8

How does HPV act as a direct carcinogen?

Answer 8

Expresses E6 and E7 proteins that inhibit p53 and pRB protein function, both of which are important for cell proliferation

Question 9

How do hep B and C act as carcinogens?

Answer 9

They are indirect carcinogens

Cause chronic liver cell injury and regeneration

Question 10

How does HIV act as a carcinogen?

Answer 10

Indirectly

Lowers immunity allowing other potentially carcinogenic infections to occur

Question 11

Conditions for sporadic retinoblastoma to occur?

Answer 11

Both hits need to be somatic mutations and to occur in the same cell. (Not inherited)

Question 12

How is familial cancer inherited?

Answer 12

First hit delivered through the germline and affects all cells. The second hit is a somatic mutation

Question 13

What are tumour suppressor genes? What changes must occur for cancer to occur?

Answer 13

Genes that inhibit neoplastic growth

Both alleles of the tumour suppressor gene need to be inactivated, explaining why two hits are needed

Question 14

What are oncogenes? What changes must occur for cancer to occur by these?

Answer 14

Genes that enhance neoplastic growth
Abnormally activated versions of proto-oncogenes
Only one allele of each proto-oncogene needs to be activated to favour neoplastic growth

Question 15

What is RAS and what does it do?

Answer 15

The first human oncogene to be discovered
RAS proto-oncogene encodes a small G protein that relays signals to the cell that eventually push it past the cell cycle restriction point

Question 16

What role does mutant RAS have in cancer?

Answer 16

Mutated in approx a third of all malignant neoplasms

In mutants, the protein is always active so there are constant signals pushing it past the restriction point.

Question 17

What is xeroderma pigmentosum?

Answer 17

Mutation in genes that affect nucleotide excision repair. Cannot repair damage caused by UV.
Sensitive to UV damage and develop skin cancer at a young age
Autosomal recessive

Question 18

What happens in familial breast carcinoma?

Answer 18

BRCA1 or BRCA2 genes are affected

They are important for repairing double strand DNA breaks

Question 19

What type of genes does hereditary non-polyposis colon cancer affect?

Answer 19

DNA mismatch repair genes

Question 20

What is genetic instability?

Answer 20

Accelerated mutation rate found in malignant neoplasms
Due to abnormal chromosome segregation during mitosis and the mutations in genes for excision repair, mismatch repair or genes repairing double strand DNA breaks.

Question 21

What is the adenoma-carcinoma sequence?

Answer 21

When something begins as a benign adenoma, but progresses to a carcinoma. This is because most malignant tumours require alterations affecting a combination of multiple tumour suppressor genes and proto-oncogenes.
Mutations accumulate

Question 22

What is progression?

Answer 22

The steady accumulation of multiple mutations

Question 23

What are the stages of the evolution of cancer?

Answer 23

Initiation
Promotion
Progression

Question 24

What are the six hallmarks of cancer?

Answer 24

Self-sufficiency in growth signals
Resistance to stop growth signals
No limit on the number of times a cell can divide (cell immortalisation)
Sustained ability to induce new blood vessels (angiogenesis)
Resistance to apoptosis
The ability to invade and produce metastases

Question 25

What is the enabling characteristic of cancer?

Answer 25

Genetic instability

Question 26

Give a summary of the model of cancer pathogenesis

Answer 26

Somatic cells exposed to environmental carcinogens which are initiators or promoters
They culminate in a monoclonal population of mutant cells
Inherited mutations in the germline can be present
Some of these clones harbour mutations affecting a PO or a TS gene.
During progression, cells acquire further activated oncogenes or inactivated TS genes, including ones that cause genetic instability
Results in a population of cells that have acquired a set of mutations that produce all of the hallmarks of cancer