Session 10

Question 1

What factors contribute to increased cancer risk?

Answer 1

Intrinsic - heredity, age and gender

Extrinsic - environment and lifestyle. 85% of a populations cancer risk. Includes chemical, radiation and infections.

Question 2

What are the 5 leading behavioural and dietary risks of cancer that lead to 30% of cancer deaths?

Answer 2

High BMI
Low fruit and veg intake
Lack of exercise
Tobacco use
Alcohol use

Question 3

What did malignant neoplasms caused by 2-napthylamine from the dye industry show?

Answer 3

There is a long delay between exposure and onset
The risk of cancer depends on carcinogen dosage
There is sometimes organ specificity for particular carcinogens (bladder for 2-napthylamine)

Question 4

What does the Ames test show and how is it carried out?

Answer 4

Shows initiators are mutagens and promotors cause prolonged proliferation in target tissue.
A rat liver extract containing cytochrome P450 is added to a salmonella strain requiring histidine. When added to a media with minimal histidine, the salmonella only grows when a possible mutagen is added. This suggests the mutagen causes mutations.

Question 5

How and where are chemical pro carcinogens converted into carcinogens?

Answer 5

By cytochrome P450 in the liver

Question 6

What is the name given to carcinogens that act as both initiators and promoters?

Answer 6

Complete carcinogens

Question 7

List the clinically important types of radiation

Answer 7

Ionising - alpha particles, beta particles, gamma rays and X rays
Electromagnetic - gamma rays, X rays and UV rays
Nuclear - alpha particles, beta particles and gamma rays

Question 8

How can radiation damage DNA?

Answer 8

Directly - altered bases or single/double strand breaks

Indirectly - generate free radicals

Question 9

How can infections cause neoplasms?

Answer 9

Directly - they can affect genes that control cell growth.
Indirectly - they can cause chronic tissue injury, where regeneration acts as either a promoter for any pre-existing mutation or causes new mutations when DNA replicates.

Question 10

How does HPV act as a carcinogen?

Answer 10

It is a direct carcinogen because it expresses E6 and E7 proteins that inhibit p53 and pRb respectively, both of which are important in cell proliferation. p53 normally causes apoptosis and pRb normally inhibits the cell cycle. Hence cells infected with HPV abnormally survive and proliferate.
HPV is linked to cervical carcinoma.

Question 11

How do the Hepatitis B and C viruses act as carcinogens?

Answer 11

They are indirect carcinogens that cause chronic liver cell injury and regeneration.

Question 12

Give an example of a bacterium and a parasite that are indirectly carcinogenic

Answer 12

Helicobacter pylori - chronic gastric inflammation

Parasitic flatworms - cause inflammation of the bile ducts and bladder mucosa, increasing the risk of carcinoma

Question 13

How does HIV act as a carcinogen?

Answer 13

Acts indirectly by lowering immunity and allowing potentially carcinogenic infections to occur

Question 14

Describe the two hit hypothesis for tumour suppressor genes using retinoblastoma as the example

Answer 14

This tumour can occur sporadically or in members of the same family.
For familial retinoblastoma (dominant inheritance), the first hit is through the germline and affected all the cells in the body. The second hit was a somatic mutation - affecting 1 in 10million retinal cells. Usually bilateral retinoblastoma.
Sporadic retinoblastoma has no germline mutation so requires both hits to be somatic mutations IN THE SAME CELL. Usually unilateral.

Question 15

Why do tumour suppressor genes need two hits but proto-oncogenes only need one?

Answer 15

Both alleles for the tumour suppressor gene need to be INACTIVATED but only one of each allele for the proto-oncogene needs to be ACTIVATED.

Question 16

How can the restriction point be deregulated by both activated oncogenes and inactivated tumour suppressor genes?

Answer 16

The RAS proto-oncogene encodes a small G protein that signals to push the cell past the cell cycle restriction point.
The Rb gene restrains cell proliferation by inhibiting passage through the restriction point (tumour suppressor gene). Both alleles need to be inactivated.

Question 17

What substances can proto-oncogenes and tumour suppressor genes encode?

Answer 17

Growth factors, growth factor receptors (oncogene HER-2), plasma membrane signal transducers, intracellular kinases, transcription factors (oncogene c-myc), cell cycle regulators and apoptosis regulators.

Question 18

What is xeroderma pigmentosum?

Answer 18

Autosomal recessive condition due to a mutation in one of the genes that causes DNA excision repair. These patients are very sensitive to UV damage and can develop skin cancer at a young age.

Question 19

What is hereditary non-polyposis colon cancer (HNPCC)?

Answer 19

Autosomal dominant condition resulting in a mutation in one of the DNA mismatch repair genes.

Question 20

What do BRACA1 and BRACA2 genes do and what neoplasm are they associated with?

Answer 20

They repair double stranded DNA breaks. Familial breast carcinoma.

Question 21

What is the function of caretaker genes?

Answer 21

They are tumour suppressor genes that maintain genetic stability and reduce the mutation rate.

Question 22

Describe the colonic adenoma-carcinoma sequence

Answer 22

A benign colonic adenoma accumulates multiple mutations, sometimes over decades, to become a colon carcinoma. This is cancer progression. Hence cancer evolves by initiation, promotion and progression.

Question 23

What are the 6 hallmarks and one enabling feature of a fully evolved malignant neoplasm?

Answer 23

Self sufficiency in growth signals
Resistance to growth stop signals
No limit on the number of times the cell can divide (cell immortalisation)
Ability to produce new blood vessels (angiogenesis)
Resistance to apoptosis
Ability to invade and produce metastases (exclusive to malignant)

Question 24

What is the main neoplasm associated with Epstein Barr virus?

Answer 24

Burkitt’s lymphoma