Photocarcinogenesis Flashcards
What is xeroderma pigmentosum?
Genetic condition which reduces the ability of the body to repair DNA damage causing a 2000 fold increase in skin cancer
Which type of skin cancers are found on chronically sun exposed sites?
Squamous cell carcinomas
Which factors are most likely to cause the development of melanomas or BCCs?
- Sunburn
- Intense intermittent or recreational UV exposure
Artificial UV (sunbeds) shows the greatest increase in which type of cancer?
Squamous cell carcinoma
What are the two major types of UVB induced DNA lesion?
- Cyclobutane pyrimidine dimers
- Pyrimidine-pyrimidine (6-4)
How is the rate of cancer development impacted by the use of TNFa inhibitor usage in conditions such as psoriasis?
Increases
How is UVA induced DNA damage repaired?
Base excision repair
(Base-free deoxyribose is cleaved away by endonuclease)
Which type(s) of skin cancer have increased incidence after exposure to certain chemicals such as coal tar pitch, soot, arsenic, shale oils etc. ?
- Basal cell carcinoma
- Squamous cell carcinoma
(Only non-melanoma skin cancers)
Which enzyme is responsible for excising oxidised bases from UVA damage?
DNA glycosylase
Which band of UV radiation directly causes DNA damage?
UVB
Which band of UV radiation penetrates deepest into the skin?
UVA
Mutations in PTCH1 are associated with which type of skin cancer?
Basal cell carcinoma
Why are fair skinned people at higher risk of developing melanoma?
More pheomelanin is produced versus eumalanin
Does not protect as well against UV
How is UVB induced DNA damage repaired?
Nucleotide excision repair
What is Ras?
Growth factor
Which gastro-intestinal condition has a strong association with malignant melanoma?
Crohn’s disease
(much higher than UC)
Pyridine dimers are formed due to exposure to which UV band?
UVB
Most skin cancers are of which class?
Non-melanoma skin cancers
What is a proto-oncogene?
Normal form of an oncogene
(not yet mutated)
UVB induced DNA damage is repaired via which method?
Nucleotide excision repair
UVA induced DNA damage is repaired via which method?
Base excision repair
How do oncogenes function normally?
Cell division will be produced only in response to growth factors (i.e. when growth is required)
TNF alpha inhibitor use has been shown to do what?
Increase the rate of cancer development
Which enzyme cleaves away a base free deoxyribose after UVA induced DNA damage?
Endonuclease
(DNA glycosylase cleaves the altered base first)
Mutations in Ras/Raf/MAPK are associated with which type of skin cancer?
Melanoma
How do pyrimidine dimers occur?
Bonding between base pairings is disrupted
Some bases bond to adjacent bases on the same DNA strand
Describe the steps taken in UVB induced DNA lesion repair
- Recognition of damaged DNA
- Cleavage of damaged DNA on either side of the photoproduct
- DNA polymerase fills the gap using the undamaged strand as a template
- DNA ligase seals the ends
Which comorbidity is most associated with melan oma?
Crohn’s disease
(UC is too but to a far lesser degree)
How does UVA cause DNA damage?
Oxidation of bases
In which 3 ways can UV cause immunosuppression?
- Depletion of Langerhans cells (reduced antigen presentating capability)
- Generation of UV induced regulatory T cells
- Secretion of anti-inflammaotry cytokines by macrophages and keratinocytes
Which two genes are associated with familial melanoma?
CDKN2A and CDK4
