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MoD > 20 Carcinogenesis > Flashcards

20 Carcinogenesis Flashcards

1
Q

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

A 
Chemicals.
Infectious agents.
Radiation.
Minerals.
Physiological.
Chronic inflammation.
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2
Q

Give two examples of chemical carcinogens:

A

PAH.

Nitrosamines.

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3
Q

Give two examples of infectious carcinogens:

A

Helicobacter pylori.

Human papilloma virus.

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4
Q

Give two examples of mineral carcinogens:

A

Asbestos.

Heavy metals.

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5
Q

Give two examples of physiological carcinogens?

A

Oestrogen.

Androgens.

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6
Q

Give two examples of carcinogens resulting from chronic inflammation:

A

Free radicals.

Growth factors.

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7
Q

What does aflatoxin cause?

A

Liver cancer.

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8
Q

Where do X-rays cause cancer?

A

Bone marrow.

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9
Q

Where does HBV cause cancer?

A

Liver.

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10
Q

Where does HPV cause cancer?

A

Cervix.

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11
Q

Define a carcinogen:

A

Any agent that significantly increases the risk of getting cancer.

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12
Q

Differentiate between initiators, promoters, and complete carcinogens:

A

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

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13
Q

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

A

Chemical modification of DNA.

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

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14
Q

How doe promoters contribute to carcinogenesis? (2).

A

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

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15
Q

Name a complete carcinogen:

A

UV light.

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16
Q

How are tumour suppressor genes commonly inactivated?

A

Aberrant methylation of gene promoter region.

17
Q

What do mutations in oncogenes lead to?

A

Gain of function.

18
Q

What do mutations in tumour suppressor genes lead to?

A

Loss of function.

19
Q

Name four direct acting carcinogens:

A

Oxygen radicals.
Nitrosamines.
UV light.
Ionising radiation.

20
Q

What are procarcinogens?

A

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

21
Q

Name two pro carcinogens:

A

Aromatic amines.

Polycyclic aromatic hydrocarbons (PAH).

22
Q

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

A

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

23
Q

What does BPDE stand for?

A

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

24
Q

What is the NER pathway?

What do defects in it lead to?

A 
Nucleotide-excision repair.
Xeroderma Pigmentosum (UV sensitivity).
25
Q

What is the ATM gene involved in?

What do defects in it lead to?

A

Recombinational repair.

Ataxia telangiectasia.

26
Q

What is Ataxia telangiectasia?

A

Autosomal recessive disorder with x100 cancer risk.

27
Q

What does the ATM gene product interact with?

A

Tumour supressor genes such as TP53 and BRCA1.

28
Q

What do defects in mismatch repair genes lead to?

A

HNPCC.

29
Q

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

A

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

30
Q

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

A 
Polycyclic aromatic hydrocarbon: benzopyrene.
Acrolein.
Nitrosamines.
Radioactive lead + polonium.
Heavy metals: cadmium, chromium.
31
Q

Where does alcohol cause cancer? (7).

A 
Mouth.
Oesophagus.
Pharynx. 
Larynx.
Breast. 
Bowel.
Liver.
32
Q

How does alcohol cause cancer? (5).

A

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).

33
Q

How does oestrogen cause cancer? (2)

A

Stimulates cell division.

Directly induces DNA damage.

34
Q

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

A 
Oral contraceptives.
Hormone replacement therapy.
Alcohol consumption.
First pregnancy >30 years.
Early menarche.
Late menopause.
Post menopausal obesity.
35
Q

How does chronic inflammation cause cancer? (2)

A

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

36
Q

What proportion of cancer deaths are due to preventable causes?

A

> 50%

MoD (21 decks)

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