Carcinogenesis

Question 1

Features of a benign tumour?

Answer 1

Slow growth
Non-invasive
No metastasis

Question 2

Features of a malignant tumour?

Answer 2

Rapid growth
Invasive
Potential for metastasis

Question 3

What are the stages of carcinogenesis?

Answer 3

Initiation
Promotion
Progression

Question 4

What happens in initiation?

Answer 4

Unrepaired DNA damage due to a carcinogenic initiator

Question 5

What happens in promotion?

Answer 5

Coronal expansion from rapid proliferation leading to benign tumour formation

Question 6

How long does promotion take?

Answer 6

10 to 30 years

Question 7

How do carcinogens cause mutations?

Answer 7

After being metabolised, it forms a DNA adduct (covalent bond) which causes a mutation

Question 8

What can be a mutagen and how do they cause the damage?

Answer 8

A virus causing insertional mutagenesis
Chemicals causing DNA adducts
UV and ionising radiation causing single and double strand breaks

Question 9

Function of a proto-oncogene?

Answer 9

Cause cell growth and gene transcription

Question 10

Normal function of a tumour suppressor gene?

Answer 10

Cell repair
Cell cycle control
Cell death

Question 11

Difference between a tumour initiator and promoter?

Answer 11

Initiators are mutagens
Promoter causes multiplication of the damaged cells
If exposed to a promoter first and then the initiator, nothing will happen

Question 12

Example of a promoter?

Answer 12

Oestrogen for breast cancer

Androgens for prostate cancer

Question 13

What can be an intracellular cause of a gene mutating?

Answer 13

Misinterpretation of code
Polymerase slippage
Base malalignment
Ineffective repair with age

Question 14

What can be environmental causes of mutations and how?

Answer 14

Carcinogens which bind to DNA and alter the sequence, affecting replication
Ionising radiation/UV can cause strand breaks or cross-links
DNA can be translocated to transcriptionally active regions

Question 15

Give examples of initiators

Answer 15

Chemical carcinogens
Oncogenic viruses
Radiation
UV light 
Oxygen free radicals

Question 16

Give examples that can cause mutations in genes

Answer 16

Alteration of bases
Strand breaks 
Base oxidation
Deletion of bases
Deletion of chromosome fragments
Adducts of carcinogen and base
Chromosome translocation/rearrangement
Gene amplification

Question 17

Examples of some chemical promoters?

Answer 17

Phorbol esters
Phenols in tobacco tar
Xenoestrogens found in insecticides
Saccharin

Question 18

Give inflammatory examples of promoters

Answer 18

Chronic irritation from eg pipe smoking
Endoparasites eg schistosoma haematobium causing bladder cancer
Bacterial infection eg H pylori

Question 19

Which drug can be given to block oestrogen receptors?

Answer 19

Tamoxifen

Question 20

What is cancer?

Answer 20

A group of diseases sharing similar characteristics, all of which show inappropriate proliferation, invasion and metastasis

Question 21

What is cell signalling required for?

Answer 21

Cell cycle progression
Proliferation
Inflammation
Pro/anti-apoptosis
Metastasis
Invasion

Question 22

What is cell signalling controlled by?

Answer 22

Cell surface receptors 
Ligands
Cascade of intracellular signal transduction 
Proteins
Transcription factors 
Inhibitors
Mitogens
Cytokines

Question 23

What can be changed about cell signalling pathways so that they promote cancer?

Answer 23

Increase in receptor expression
Mutant receptor expression (self-activating)
Down-regulation of inhibitory proteins/mechanisms
Increased ligand expression
Increased expression of transcription factors

Question 24

What are the six hallmarks of cancer and how does it do it?

Answer 24

Induce angiogenesis - active VEGF signalling

Evade growth suppressors - inactivate cell cycle checkpoint

Sustain proliferative signalling - constitutively activate growth factor signalling

Activate invasion and metastasis - loss of cell-to-cell interactions

Replicative immortality - inactivated cell death pathway

Resistance to cell death - activated anti-cell death signalling

Question 25

Other than the six hallmarks of cancer, what are 4 more important features recently discovered?

Answer 25

Tumour-promoting inflammation Avoid immune destruction Genome instability and mutation Deregulating cellular energetics

Question 26

General risk factors for cancer?

Answer 26

``` Genes Carcinogens Radiation Chemicals eg abestos Viruses eg HPV Diet Alcohol Smoking ```

Question 27

What are some carcinogens in different foods?

Answer 27

``` Heterocyclic amines (meat) Toxins Inflammation/oxidative stress inducers Hot drinks/food Alcohol ```

Question 28

Which foods specifically are carcinogens?

Answer 28

``` Red meat Animal fat Salted fish BBQ/chargrilled foods Salt-preserved foods Contaminated foods (fungus) ```

Question 29

What evidence is there that foods affect cancer risk?

Answer 29

Migration studies | Intervention trials

Question 30

What increases heterocyclic amine concentration?

Answer 30

Cooking meat and increasing the cooking time | Metabolised to the liver to genetoxic metabolites

Question 31

How does barbecuing meat increase cancer risk?

Answer 31

Burns fat to produce polyaromatic hydrocarbons which require metabolic activation Adducts to DNA bases - p53

Question 32

How do high carb foods increase cancer risk?

Answer 32

If they are roasted or baked eg cereal, coffee, bread, crisps Contain acrylamide which is a genotoxic metabolite which adducts to DNA

Question 33

What is chemoprevention?

Answer 33

Inhibition, retardation or reversal of the carcinogenic process

Question 34

Examples of drugs in chemoprevention?

Answer 34

Tamoxifen Celecoxib (COX-2) Aspirin (COX) Herceptin (EGFR Ab)

Question 35

What is a direct acting carcinogen?

Answer 35

One that binds directly to DNA

Question 36

What are procarcinogens?

Answer 36

Require metabolic activation