20 Carcinogenesis

Question 1

What are the categories of human carcinogens? (6).

Answer 1

Chemicals.
Infectious agents.
Radiation.
Minerals.
Physiological.
Chronic inflammation.

Question 2

Give two examples of chemical carcinogens:

Answer 2

PAH.

Nitrosamines.

Question 3

Give two examples of infectious carcinogens:

Answer 3

Helicobacter pylori.

Human papilloma virus.

Question 4

Give two examples of mineral carcinogens:

Answer 4

Asbestos.

Heavy metals.

Question 5

Give two examples of physiological carcinogens?

Answer 5

Oestrogen.

Androgens.

Question 6

Give two examples of carcinogens resulting from chronic inflammation:

Answer 6

Free radicals.

Growth factors.

Question 7

What does aflatoxin cause?

Answer 7

Liver cancer.

Question 8

Where do X-rays cause cancer?

Answer 8

Bone marrow.

Question 9

Where does HBV cause cancer?

Answer 9

Liver.

Question 10

Where does HPV cause cancer?

Answer 10

Cervix.

Question 11

Define a carcinogen:

Answer 11

Any agent that significantly increases the risk of getting cancer.

Question 12

Differentiate between initiators, promoters, and complete carcinogens:

Answer 12

Initiator: chemically modifies DNA.
Promoter: induces proliferation.
Complete: an initiator and promoter.

Question 13

What does mutation induction (initiation) require? (2).

Answer 13

Chemical modification of DNA.

Replication of modified DNA and mis-incorporation of DNA polymerase.

Question 14

How doe promoters contribute to carcinogenesis? (2).

Answer 14

Stimulate two rounds of DNA replication required for mutation fixation.
Stimulate clonal expansion of mutated cells.

Question 15

Name a complete carcinogen:

Answer 15

UV light.

Question 16

How are tumour suppressor genes commonly inactivated?

Answer 16

Aberrant methylation of gene promoter region.

Question 17

What do mutations in oncogenes lead to?

Answer 17

Gain of function.

Question 18

What do mutations in tumour suppressor genes lead to?

Answer 18

Loss of function.

Question 19

Name four direct acting carcinogens:

Answer 19

Oxygen radicals.
Nitrosamines.
UV light.
Ionising radiation.

Question 20

What are procarcinogens?

Answer 20

Carcinogens which require enzymatic activation before they can interact with DNA.

Question 21

Name two pro carcinogens:

Answer 21

Aromatic amines.

Polycyclic aromatic hydrocarbons (PAH).

Question 22

Benzopyrene is a pro-carcinogen, how does it become a carcinogen?

Answer 22

Reaction with P450 mixed function oxidases and epoxide hydrolase.
Becomes BPDE.

Question 23

What does BPDE stand for?

Answer 23

Benzo pyrene 7,8-diol, 9,10-epoxide.

Question 24

What is the NER pathway?

What do defects in it lead to?

Answer 24

Nucleotide-excision repair.
Xeroderma Pigmentosum (UV sensitivity).

Question 25

What is the ATM gene involved in? | What do defects in it lead to?

Answer 25

Recombinational repair. | Ataxia telangiectasia.

Question 26

What is Ataxia telangiectasia?

Answer 26

Autosomal recessive disorder with x100 cancer risk.

Question 27

What does the ATM gene product interact with?

Answer 27

Tumour supressor genes such as TP53 and BRCA1.

Question 28

What do defects in mismatch repair genes lead to?

Answer 28

HNPCC.

Question 29

Why do the same levels of carcinogen exposure lead to different levels of cancer?

Answer 29

Genetic variation in metabolic enzymes, DNA repair genes and detoxification/excretion.

Question 30

Which carcinogens are present in tobacco smoke? (5).

Answer 30

``` Polycyclic aromatic hydrocarbon: benzopyrene. Acrolein. Nitrosamines. Radioactive lead + polonium. Heavy metals: cadmium, chromium. ```

Question 31

Where does alcohol cause cancer? (7).

Answer 31

``` Mouth. Oesophagus. Pharynx. Larynx. Breast. Bowel. Liver. ```

Question 32

How does alcohol cause cancer? (5).

Answer 32

Converted to acetaldehyde (direct damage). Increases levels of oestrogen + testosterone. Increases uptake of carcinogens in GI tract. Reduces folate levels (accuracy decreases). Kills surface epithelium (proliferation).

Question 33

How does oestrogen cause cancer? (2)

Answer 33

Stimulates cell division. | Directly induces DNA damage.

Question 34

What are the risk factors for breast cancer related to oestrogen exposure? (7).

Answer 34

``` Oral contraceptives. Hormone replacement therapy. Alcohol consumption. First pregnancy >30 years. Early menarche. Late menopause. Post menopausal obesity. ```

Question 35

How does chronic inflammation cause cancer? (2)

Answer 35

Initiation: free radical release by immune cells. Promotion: growth factor induced cell division.

Question 36

What proportion of cancer deaths are due to preventable causes?

Answer 36

> 50%