Lect 20 - Carcinogenesis: Causes of Cancer

Question 1

what are the Categories of human carcinogens?

Answer 1

Chemicals
Infectious agents (H. Pylori)
Radiation
Minerals (heavy metals)
Physiological (oestrogen)
Chronic inflammation (free radicals and growth factors)

Question 2

what does Aflatoxin target?

Answer 2

liver

Question 3

what does Alcohol target?

Answer 3

pharynx, larynx, oesoph., liver

Question 4

what does Asbestos target?

Answer 4

lung pleura

Question 5

what do Xrays target?

Answer 5

bone marrow (leukaemia)

Question 6

what does UV-light target?

Answer 6

skin

Question 7

what does Oestrogen target?

Answer 7

breast

Question 8

what does Tobacco smoke target?

Answer 8

mouth, lung, oesophagus,

pancreas, kidney, bladder, etc.

Question 9

what does HBV target ?

Answer 9

liver

Question 10

what does HPV target ?

Answer 10

cervix

Question 11

what is a carcinogen?

Answer 11

Any agent that significantly increases the risk of developing cancer

Question 12

what are INITIATORS?

Answer 12

Carcinogens that are genotoxic i.e. can chemically modify or damage DNA

Question 13

what are PROMOTERS?

Answer 13

non-genotoxic Carcinogens e.g. induce proliferation and DNA replication

Question 14

what are “complete” carcinogens?

Answer 14

carcinogen that can initiate and promote e.g. UV light

Question 15

what does Mutation induction (initiation) require?

Answer 15

Chemical modification of DNA

Replication of modified DNA and mis-incorporation by DNA polymerase

Question 16

name some Common genetic abnormalities (4)

Answer 16

Base pair substitution
Frameshift
Deletion
Gene amplification

Question 17

what can cause tissue suppressor genes to be epigenetically under expressed?

Answer 17

Aberrent methylation.

Question 18

what do mutations in oncogenes cause?

Answer 18

gain of function - amplification

Question 19

what does loss of TSGs lead to?

Answer 19

loss of function - inability to prevent amplification

Question 20

what is a Procarcinogen?

Answer 20

an agent that requires enzymatic (metabolic) activation before they react with DNA, e.g. aromatic amines, polycyclic aromatic hydrocarbons (PAHs)

Question 21

what Defences against carcinogenesis are there?

Answer 21

Dietary antioxidants
Detoxification mechanisms
DNA repair enzymes
Apoptotic response to unrepaired genetic damage
Immune response to infection and abnormal cells

Question 22

how many identified carcinogens are there in tobacco smoke?

Answer 22

19

In combination with promotion by alcohol leads to 100-fold increased risk for head & neck cancer

Question 23

how does alcohol cause DNA damage?

Answer 23

it is converted into acetaldehyde, which can cause DNA damage.

increases levels of oestrogen and testosterone

increases uptake of carcinogenic chemicals

reduces levels of folate, needed for accurate DNA replication

can kill surface epithelium leading to unscheduled proliferation

Question 24

give examples of types of chronic inflammation that are important in causing cancer.

Answer 24

colitis, hepatitis, Barrett’s metaplasia, gastritis, gallstones