Photocarcinogenesis

Question 1

What is the definition of cancer?

Answer 1

An accumulation of abnormal cells that multiply through uncontrolled cell division and spread to other parts of the body by invasion and/or distant metastasis via the blood and lymph system

Question 2

What are the hallmarks of cancer?

Answer 2

Sustaining proliferative signalling 
Evading growth suppressors
Activating invasion and metastasis 
Enabling replicating immortality 
Inducing angiogenesis 
Resisting cell death

Question 3

What are the emerging hallmarks and enabling characteristics of cancer?

Answer 3

Avoiding immune destruction
Tumour promoting inflammation
Genome instability and mutation
Deregulating cellular energetics

Question 4

What is an oncogene?

Answer 4

Over active form of a gene that positively regulates cell division
Drives tumour formation when activity or copy number is increased e.g. Ras, raf or growth factor receptors

Question 5

What is a tumour suppressor gene?

Answer 5

Inactive or non functional form of a gene that negatively regulate cell division - Rb, p53

Question 6

What is important to understand in sun exposure in relation to risk of skin cancer?

Answer 6

Dose and pattern
Latitude
Sunburn in childhood
Intense intermittent exposure vs chronic life long UV exposure

Question 7

What type of sun exposure predisposes to SCC?

Answer 7

Life long cumulative UV exposure

Question 8

What type of sun exposure predisposes to melanomas and BCC?

Answer 8

Intermittent burning episodes of sun exposure

Sun bed use

Question 9

Exposure to which chemicals can increase the risk of NMSC?

Answer 9

Coal tar pitch 
Soot
Creoste
Petroleum products
Shale oils
Arsenic

Question 10

What type of DNA damage does UVB radiation lead to?

Answer 10

Direct DNA damage
CPDs
Pyramidine pyramidine 6-4 photo products
Repaired by NER 
CC-TT UV signature mutation

Question 11

What type of DNA damage does exposure to UVA sun do?

Answer 11

Oxidation of deoxyguanosine forming 8-oxo depxyguanosine
Repaired by base excision repair
C-A point mutation

Question 12

How does UV act in an immunosuppressive way?

Answer 12

Depletion of langerhans cells skin and reduce ability to present antigens
Generation of UV induced and regulatory T cells with immunosuppressive activity
Secretion of anti-inflammatory cytokines like IL-10

Question 13

What mutations are important in the development of BCC?

Answer 13

PTCH1 which is a key component in the hedgehog signalling pathway - this pathway induces cell proliferation and angiogenesis

Question 14

What mutations are important in melanoma?

Answer 14

Ras/raf/MAPK
Vemurafenib targets B-raf
Tramatenib targets MEK
There are familial melanomas that alter the activity of CDK4