Photocarcinogenesis Flashcards

1
Q

how is cancer defined?

A

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

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2
Q

how does cancer arise?

A

multi-step gene damage via clonal evolution

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3
Q

describe the process of clonal evolution

A

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

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4
Q

what is field cancerization?

A

field of mutated cells

multiple different tumours can arise

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5
Q

what is dynamic clonal diversification?

A

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

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6
Q

what are the 6 hallmarks of cancer?

A
evade growth suppressors
activating invasion and metastases
enabling replicative immortality
inducing angiogenesis
resisting cell death
sustaining proliferative signalling
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7
Q

name 4 emerging and enabling characteristics of cancer

A

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

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8
Q

what is an oncogene?

A

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

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9
Q

what is a proto-oncogene?

A

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

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10
Q

what is a tumour suppressor?

A

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

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11
Q

how does RAS work?

A

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

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12
Q

how does P53 work?

A

switched on if theres DNA damage

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

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13
Q

is childhood sunburn more dangerous than adult sunburn?

A

yes

increases skin cancer risk 4X

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14
Q

why is skin type 1 more at risk

A

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

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15
Q

where is SCC usually found?

A

head, neck, hands, forearms

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

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16
Q

what type of exposure is associated with melanoma and BCC?

A

intermittent burning episodes

sunbeds

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17
Q

when does most sun damage occur?

A

80% before 18 years old

18
Q

exposure to what chemicals can increase skin cancer risk?

A
coal tar
soot
arsenic
shale oils
petrol
creosote
19
Q

which causes acute sun damage (tan, burn)?

20
Q

which UV is filtered by windows?

21
Q

which UV is more damaging?

A

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

22
Q

how does UVA damage?

A

causes indirect damage via oxidative damage
causes ageing etc
always present

23
Q

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

A

pyrimidine dimer

covalent bonding between adjacent pyrimidines on the same DNA strand

24
Q

what are the 2 types of pyrimidine dimer?

A

cyclobutene pyrimidine dimers (CPDs - more common)

6,4 photo products (more damaging)

25
how are CPDs and 6-4PPs removed?
nucleotide excision repair (NER) removes the dimer and polymerase replaces it with the correct bases (but is error prone)
26
what happens when UV induced photoproducts (CPDs and 6-4PPs) aren't removed?
interfere with base pairing during DNA replication causing mutations (CC to TT)
27
how does UVA cause indirect damage?
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)
28
how are 8-oxo-dG lesions repaired?
oxidised bases repaired by base excision repair (BER)
29
how does chronic UV exposure affect immune system?
immunosuppressive causes antigen presenting cells to lose ability to present causes keratinocytes to secrete immunosuppressive molecules generation of immune suppressive regulatory T cells
30
mutation of what gene causes 90% of BCCs?
PTCH | activates hedgehog signalling
31
what type of cancer does chronic/long term sun exposure cause?
SCC
32
what type of cancer does intense intermittent/recreational sun exposure cause?
melanoma | BCC
33
what type of cancer does burning cause?
melanoma | BCC
34
what type of cancer does artificial UV cause?
SCC BCC melanoma
35
what does hedgehog signalling do?
leads to induction of cell proliferation genes and angiogenesis activators
36
what is vismodegib?
hedgehog inhibitor | blocks hedgehog signalling and prevents cell cycle activation and angiogenesis
37
what mutations are common in melanomas?
RAS/Raf/MAPK signalling pathways
38
what do dasatinib and imatinib inhibit?
c-Kit
39
what do vemurafenib and dabrafenib inhibit?
B-Raf
40
what does trametinib inhibit?
MEK
41
what 2 genes have been linked to familial melanoma?
CDKN2A | CDK4