Photocarcinogenesis

Question 1

describe what an oncogene is

Answer 1

over-active form of a gene that positively regulates cell division, drives tumour formation when activity or copy number is increased
(accelerator)

Question 2

describe what a proto-oncogene is

Answer 2

the normal, not yet mutated, form of an oncogene

Question 3

describe what a tumour suppressor is

Answer 3

inactive or non-functional form of a gene that negatively regulates cell division, prevents formation of a tumour when functioning properly
(brake)

Question 4

describe the role of p53

Answer 4

tumour suppressor

cell cycle arrest, DNA repair, block of angiogenesis, apoptosis

Question 5

describe the effect sun-exposure has on p53

Answer 5

increase in p53 ‘clones’(mutations), drives clonal expansion of mutant p53 cells

Question 6

what are the risk factors for ski cancer

Answer 6

UV exposure, genetics, age, chemical exposure, immune suppression

Question 7

describe how UVA and UVB increase cancer risk

Answer 7

UVB = causes DIRECT DNA damage
UVA = causes INDIRECT oxidative damage, penetrates more deeply in skin
(UV-induced immunosuppression also plays a role)

Question 8

describe the type of sun exposure that increases risk of skin cancer

Answer 8

dose and pattern of sun-exposure, latitude, sunburn in childhood, intense intermittent exposure or chronic life-long UV exposure

Question 9

what skin type is more at risk of skin cancer

Answer 9

pale skin, poor tanning skin, easy burning skin

Question 10

describe why paler skin increases risk of skin cancer development

Answer 10

Pheomelanin in skin rather than Eumelanin, phaeomelanin absorbs UV radiation less efficiently, unable to “tan” in protective way

Question 11

what sun exposure patterns are associated with melanoma and basal cell carcinoma

Answer 11

intermittent burning episodes of sun exposure, and sunbeds also increase risk

Question 12

what sun exposure patterns are associated with squamous cell carcinoma

Answer 12

lifetime cumulative UV exposure

Question 13

of UVA and UVB exposure which is worse and which is more prevalent

Answer 13

UVA much more prevalent

UVB 1000 times more damaging, only when sun directly overhead

Question 14

what type of mutation is caused by UV exposure

ie insertion, deletion etc.

Answer 14

pyrimidine dimer, formed by covalent bonding between adjacent pyrimidnes on the same DNA strand

Question 15

what are the 2 major types of UVB-induced DNA lesion

Answer 15

cyclobutane pyrimidine dimers(CPDs) and pyrimidine-pyrimidone(6-4)photo-products

(CPD 3 times more common)

Question 16

what removes CPD and 6-4PP mutations in normal DNA repair

Answer 16

nucleotide excision repair(NER)

Question 17

describe how UVA can cause indirect DNA damage

Answer 17

via oxidation of DNA bases, especially deoxyguanosine to form 8-oxo-deoxyguanosine

Question 18

what removes oxidised bases in normal DNA repair

Answer 18

base excision repair(BER)

Question 19

describe how UV induced DNA damage also leads to immunosuppression

Answer 19

depletes Langerhans cells in skin so reduced ability to present antigens, generation of UV induced T cells with immune suppressive activity , and secretion of anti-inflammatory cytokines

Question 20

what are the immune suppressive risk factors for skin cancer

Answer 20

inflammatory or autoimmune conditions(eg UC or Crohn’s), immunosuppressant drugs, organ transplant recipients

Question 21

what chemical exposure can increase risk of non-melanoma skin cancer development

Answer 21

coal tar pitch, soot, arsenic, petroleum products

Question 22

what phototoxic drugs increase risk of skin cancer

Answer 22

voriconazole(antifungal), thiazides, NSAIDs, anti-TNF, azathioprine