Photocarcinogenesis

Question 1

how is cancer defined?

Answer 1

accumulated of abnormal cells that multiply through uncontrolled cell division and spread to other parts of the bpdy via blood and lymphatics

Question 2

how does cancer arise?

Answer 2

multi-step gene damage via clonal evolution

Question 3

describe the process of clonal evolution

Answer 3

mutation in generation 1 passes to generation 2 cells
1 gen 2 cells might develop a second mutation and pass iton etc until enough mutation have acquired to form a cancerous cell

Question 4

what is field cancerization?

Answer 4

field of mutated cells

multiple different tumours can arise

Question 5

what is dynamic clonal diversification?

Answer 5

a single mutation acts as a driver mutation that causes the issues - e.g increased mutation rate

Question 6

what are the 6 hallmarks of cancer?

Answer 6

evade growth suppressors
activating invasion and metastases
enabling replicative immortality
inducing angiogenesis
resisting cell death
sustaining proliferative signalling

Question 7

name 4 emerging and enabling characteristics of cancer

Answer 7

avoiding immune destruction
tumour-promoting inflammation
genome instability and mutation
deregulating cellular energetics

Question 8

what is an oncogene?

Answer 8

over active form of gene causes increased cell proliferation driving tumour formation
E.g - RAS

Question 9

what is a proto-oncogene?

Answer 9

normal version of an oncogene that isn’t overactive and causing cancer

Question 10

what is a tumour suppressor?

Answer 10

inactive or non-functional form of gene causes unregulated cell division
normally functioning gene prevents tumour formation
P53
Rb

Question 11

how does RAS work?

Answer 11

attached to cell membrane, switched on when growth factor encountered causing cell division and proliferation
oncogene version always switched on even without stimulation

Question 12

how does P53 work?

Answer 12

switched on if theres DNA damage

binds to DNA causing cell cycle arrest, activation of DNA repair mechanisms or triggers apoptosis

Question 13

is childhood sunburn more dangerous than adult sunburn?

Answer 13

yes

increases skin cancer risk 4X

Question 14

why is skin type 1 more at risk

Answer 14

they produce wrong type of melanin
pheomelanin doesn’t protect as much as eumelanin
pheomelanin produces yellowish pigment and freckles

Question 15

where is SCC usually found?

Answer 15

head, neck, hands, forearms

ageing population as SCCs arise from life-long cumulative UV exposure

Question 16

what type of exposure is associated with melanoma and BCC?

Answer 16

intermittent burning episodes

sunbeds

Question 17

when does most sun damage occur?

Answer 17

80% before 18 years old

Question 18

exposure to what chemicals can increase skin cancer risk?

Answer 18

coal tar
soot
arsenic
shale oils
petrol
creosote

Question 19

which causes acute sun damage (tan, burn)?

Answer 19

UVA

Question 20

which UV is filtered by windows?

Answer 20

UVB

Question 21

which UV is more damaging?

Answer 21

UVB
as can be directly damage DNA
only really present in summer

Question 22

how does UVA damage?

Answer 22

causes indirect damage via oxidative damage
causes ageing etc
always present

Question 23

what is the most common type of damage caused to DNA by sunlight?

Answer 23

pyrimidine dimer

covalent bonding between adjacent pyrimidines on the same DNA strand

Question 24

what are the 2 types of pyrimidine dimer?

Answer 24

cyclobutene pyrimidine dimers (CPDs - more common)

6,4 photo products (more damaging)

Question 25

how are CPDs and 6-4PPs removed?

Answer 25

nucleotide excision repair (NER) removes the dimer and polymerase replaces it with the correct bases (but is error prone)

Question 26

what happens when UV induced photoproducts (CPDs and 6-4PPs) aren’t removed?

Answer 26

interfere with base pairing during DNA replication causing mutations (CC to TT)

Question 27

how does UVA cause indirect damage?

Answer 27

oxidation of DNA bases forming 8-oxo-deoxyguanosine which can form a base pair with the wrong thing causing a point mutation (C to A)

Question 28

how are 8-oxo-dG lesions repaired?

Answer 28

oxidised bases repaired by base excision repair (BER)

Question 29

how does chronic UV exposure affect immune system?

Answer 29

immunosuppressive
causes antigen presenting cells to lose ability to present
causes keratinocytes to secrete immunosuppressive molecules
generation of immune suppressive regulatory T cells

Question 30

mutation of what gene causes 90% of BCCs?

Answer 30

PTCH

activates hedgehog signalling

Question 31

what type of cancer does chronic/long term sun exposure cause?

Answer 31

SCC

Question 32

what type of cancer does intense intermittent/recreational sun exposure cause?

Answer 32

melanoma

BCC

Question 33

what type of cancer does burning cause?

Answer 33

melanoma

BCC

Question 34

what type of cancer does artificial UV cause?

Answer 34

SCC
BCC
melanoma

Question 35

what does hedgehog signalling do?

Answer 35

leads to induction of cell proliferation genes and angiogenesis activators

Question 36

what is vismodegib?

Answer 36

hedgehog inhibitor

blocks hedgehog signalling and prevents cell cycle activation and angiogenesis

Question 37

what mutations are common in melanomas?

Answer 37

RAS/Raf/MAPK signalling pathways

Question 38

what do dasatinib and imatinib inhibit?

Answer 38

c-Kit

Question 39

what do vemurafenib and dabrafenib inhibit?

Answer 39

B-Raf

Question 40

what does trametinib inhibit?

Answer 40

MEK

Question 41

what 2 genes have been linked to familial melanoma?

Answer 41

CDKN2A

CDK4