3) Carcinogenesis

Question 1

What proportion of people will get a cancer?

Answer 1

33%

Question 2

What proportion of people will die of a cancer?

Answer 2

25%

Question 3

Why is the incidence of cancer increasing?

Answer 3

Changes in lifestyle, increasing age and better screening

Question 4

What are the stages of carcinogenesis?

Answer 4

Initiation, promotion, transformation (potential regression), evolution (drug resistant), metastasis

Question 5

Give examples of mutations involved in colorectal carcinogenesis:

Answer 5

Inactivation of APC - increase in stem cells
Activation of RAS - increased proliferation
Inactivation of p53

Question 6

What are some environmental causes of gene mutation?

Answer 6

Carcinogens bind to DNA and alter sequence
Ionising radiation/UV causing strand breaks and cross links
DNA translocation

Question 7

What are some intracellular causes of gene mutation?

Answer 7

Misinterpretation of code, polymerase slippage, ineffective repair

Question 8

What are some initiating stimuli for cancers?

Answer 8

Chemical carcinogens
Oncogenic viruses e.g. HPV
Radiation, UV and radicals
Replication errors

Question 9

Give examples of direct acting carcinogens:

Answer 9

Alkylating and acylating agents e.g. dichloromethane

Cytotoxic drugs e.g. used in lymphoma and leukaemia

Question 10

Give examples of pro-carcinogens:

Answer 10

Often in tobacco, body metabolises them into active form
Polycylic aromatic hydrocarbons e.. benzopyrene
Combustion of organic compounds e.g. coal, tobacco

Question 11

In what ways can genes be mutated?

Answer 11

Alteration/deletion of bases
Strand break 
Bases oxidation
Adducts of carcinogen and base
Chromosome rearrangment or deletion 
Gene amplification

Question 12

What are clastogens?

Answer 12

Structural chromosomal changes e.g. translocation, deletion

Question 13

What are aneugens?

Answer 13

Genome mutations e.g. aneuploidy

Question 14

How can adducts cause mutation?

Answer 14

Reactive molecules bind to nucleophilic sites on DNA bases and cause slippage or prevent repair

Question 15

Describe excision repair:

Answer 15

Error free removal of modified bases by DNA glycosylases. Nucleotide excision removes bases with bulky adducts

Question 16

Describe error prone repair:

Answer 16

Response to severe DNA damage. DNA polymerases recognises specific lesions and restore original sequence

Question 17

Describe mismatch repair:

Answer 17

Proofreading by exonuclease part of DNA polymerase which corrects mismatched bases

Question 18

Give examples of promoting agents:

Answer 18

Chemical promoters - phenols in tobacco tar, saccharin
Hormones
Inflammation - pipe smoking
Microbial infection - H. pylori

Question 19

What is the bad luck hypothesis?

Answer 19

Only 1/3rd of cancer risk is due to environmental factors and inherited predispositions. Majority is due to bad luck, random mutations

Question 20

What things increases our risk of getting cancer?

Answer 20

Hereditary 
Carcinogens
Radiation - UV and ionising
Chemicals - asbestos
Viruses - HPV
Diet - alcohol 
Smoking

Question 21

How is obesity linked to cancer?

Answer 21

High BMI increases risk and obesity causes a low level inflammation (promotion)

Question 22

What foods can cause a higher risk of cancer?

Answer 22

Red meat, salted fish, BBQ food, salt-preserved food, fungus

Question 23

What are heterocyclic amines?

Answer 23

Highly mutagenic molecules that are produced when we cook meat. They are absorbed and metabolised by liver to genotoxic metabolites.

Question 24

How can we reduce our levels of heterocyclic amines?

Answer 24

Marinating and reducing cooking time of red meat reduces HA levels