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Year 2 EMS MoD > Causes of cancer > Flashcards

Flashcards in Causes of cancer Deck (53):
1

What are the 5 ways of identifying human carcinogens?

1) Geographical variation in risk - studies in migrant populations
2) Occupational exposure
3) Accidental exposure
4) Big epidemiological surveys
5) Laboratory experiments

2

What are the categories of carcinogens? 6

1) Chemicals eg. PAHs, nitrosamines
2) Infectious agents eg. HPV, H pylori
3) Radiation eg. UV light, radon
4) Minerals eg. asbestos, heavy metals
5) Physiological eg. oestrogen, androgens
6) Chronic inflammation - free radicals and growth factors

3

Aflatoxin targets what tissue?

Liver

4

Alcohol targets what 4 tissues?

Pharynx, larynx, oesophagus, liver

5

Asbestos targets what tissue?

Lung pleura

6

X-rays target what tissue?

Bone marrow (leukaemia)

7

UV light targets what tissue?

Skin

8

Oestrogen targets what tissue?

Breast

9

Tobacco smoke targets what 6 tissues?

Mouth, lung, oesophagus, pancreas, kidney, bladder etc.

10

HBV targets what tissue?

liver

11

HPV targets which tissue?

Cervix

12

What is meant by the term carcinogen?

Any agent that significantly increases the risk of developing cancer

13

What is the difference between initiator, promotor and complete carcinogens?

Initiators are genotoxic i.e. can chemical modify or damage DNA
Promotors are non genetic and induce proliferation and DNA replication
Complete carcinogens can do both

14

Name a complete carcinogen?

UV light

15

What 2 things does mutation indiction (initiation) require?

Chemical modification of DNA
Replication of modified DNA and mis-incorporation by DNA polymerase - requires 2 rounds of replication for a mutations to be fixed

16

The presence of what in the DNA exacerbates the tendency of polymerase to make mistakes?

Chemical modifications - miscoding or non-coding adducts or lesions

17

In which 2 ways do promotor carcinogens contribute to carcinogenesis?

1) They can stimulate the 2 rounds of DNA replication required for mutation fixation
2) Secondly they can stimulate clonal expansion of mutated cells, which enables the accumulation of further mutations

18

Why is clonal expansion of a cell with 1 mutation so important in carcinogenesis?

To form a malignant cell need 2-8 specific mutations, very hard for a cell to acquire these without significant clonal expansion

19

Give 2 examples of endogenous mutagens?

1) Oxygen radicals
2) Lipid metabolism byproducts

20

Describe the process of initiation, promotion and progression using a mouse model skin tumour?

1) Genotoxic initiating agent damages DNA
2) Promoting agent fixes the damage as a mutation and converts normal calls into mutant initiated cell
3) Promoting agent stimulates clonal expansion of initiated cells to produce papillomas
4) Further rounds of mutations and clonal expansion allows papilloma to progress to carcinoma

21

Give the 7 common genetic abnormalities?

1) Base pair substitution
2) Frameshift
3) Deletion
4) Gene amplification (having up to a hundred copies of a gene it would normally only have 2 copies of)
5) Chromosomal translocation
6) Chromosomal inversion
7) Aneuploidy

22

What is meant by a TSG?

Tumour suppressor gene

23

What is the most common TSG inactivation event?

Abberant methylation of gene promotor

24

What is meant by CpG islands and what role do they have in TSG inactivation?

Approximately 70% of genes have CpG islands associated with their promoter sequence, CpG methylation is only effective in shutting down the expression of a gene if it occurs within the promotor sequence of the gene - this is how TSGs are inactivated

25

Give 4 mutations that occur in oncogenes?

1) Base pair substitutions
2) Amplification
3) Translocation eg. proto-oncogene moved to an area where the genes are more frequently expressed thus ends up expressed more frequently to
4) Inversions

26

What do mutations in oncogenes lead to?

A gain of function

27

What do mutations in TSGs lead to?

Loss of function

28

Give 7 types of mutation which can occur in TSGs?

1) Base pair substitutions
2) Frameshifts
3) Deletions
4) Insertions
5) Chromosomal rearrangements
6) Chromosome loss
7) Promoter methylation

29

What is meant by a direct activating carcinogen? Give 4 examples.

Interact directly with DNA:
1) Oxygen radicals
2) Nitrosamines
3) UV light
4) Ionising radiation

30

What is meant by a procarcinogen?

Carcinogens which require enzymatic (metabolic) activation before they react with DNA, though not yet carcinogenic they are often toxic and its the enzymes that normally function in the detoxification and excretion of toxic chemicals which are normally implicated in their activation

31

How can the process of metabolic activation of procarcinogens present a genetic influence on the formation of a malignant tumour?

Enzymes involved in activation of procarcinogens are normally those involved in excretion and detoxification. People who have enzymes which activate a particular chemical more efficiently are more likely to get cancer as are those which excrete the activated chemical less efficiently

32

Name 2 procarcinogens?

1) Aromatic amines
2) Polycyclic aromatic hydrocarbons (PAHs)

33

Which enzymes are involved in the conversion of Benzopyrene to BDPE and thus the activation of benzopyrene a procarcinogen?

P450 mixed function oxidases and epoxide hydrolase

34

How does BDPE damage DNA and how is Benzopyrene produced?

Benzopyrene is generated through the combustion of most organic material such as meat, tobacco and fuel
BDPE forms a DNA adduct

35

Mutational defects in mismatch repair enzymes gives a predisposition to what disease?

Hereditary non polyposis colorectal cancer, also known as Lynch syndrome

36

Mutational defects in recombinational repair proteins gives a predisposition to what disease?

Ataxia telangiectasia

37

Mutational defects in nucleotide-excision repair proteins gives a pre-disposition to what disease?

Xeroderma pigmentosum

38

Genetic polymorphisms in genes encoding which 3 types of enzyme involved in the process from carinogen exposure to cancer may confer greater or lesser susceptibility to the effects of carcinogenic exposure?

1) Metabolic activation enzymes
2) Detoxification/ Excretion enzymes
3) DNA repair eznymes

39

Give 5 of the bodies defences against cancer?

1) Dietary antioxidants
2) Detoxification mechanisms
3) DNA repair enzymes
4) Apoptotic response to unrepaired genetic damage
5) Immune response to infection and abnormal cells

40

How many carcinogens have been identified in tobacco smoke?

19

41

Give 5 carcinogens which have been found in tobacco smoke?

1) Polycyclic aromatic hydrocarbons eg. benzopyrene, require metabolic activation
2) Acrolein - acrid smell, potent direct-actin mutagen
3) Nitrosamines - formed during curing of leaves
4) Radioactive lead and polonium
5) Heavy metals - cadmium, chromium

42

In combination with promotion by alcohol tobacco smoke leads to what increased risk for head and neck cancer?

100 fold increased risk

43

Alcohol is linked to what 7 cancers?

1) Oral
2) Oesophageal
3) Bowel
4) Liver
5) Pharynx
6) Larynx
7) Breast

44

Alcohol is converted into what substance which can cause DNA damage?

Acetaldehyde

45

Alcohol increases the levels of which 2 hormones?

oestrogen and testosterone

46

How does alcohol affect the cells of the upper GI system?

Increases uptake of carcinogenic chemicals into cells within the upper GI system

47

How can alcohol affect surface epithelium what does this lead to?

Can kill surface epithelium leading to unscheduled proliferation - increases chance of mutation

48

Alcohol reduces levels of what chemical needed for accurate DNA replication?

Reduces levels of folate

49

All of the strongest risk factors for breast cancer are associated with what?

Increased exposure to oestrogen which can both stimulate cell division and induce DNA damage

50

Give 7 breast cancer risk factors?

1) HRT
2) Oral contraception
3) Alcohol consumption
4) Age of 1st pregnancy >30 years
5) Early menarche
6) Later menopause
7) Post-menopausal obesity

51

Why does chronic inflammation play an important role in cancer?

The inflammatory response results in a double hit:
1) DNA damage from release of free radicals by immune cells - initiation
2) Growth factor induced cell division to repair tissue damage - promotion

52

What proportion of cancer deaths are attributable to environmental or behavioural factors ie preventable causes?

>50%

53

What role can diet play in cancer incidence?

In some cases diet leads to exposure to carcinogens eg. red meat, burnt food, heavy metals and in some its the absence of protective factors which can lead to the increased cancer incidence eg. fibre and antioxidants.