Lecture 22 - Prevention Of Skin Cancer Flashcards
Skin cancer stats
- life time risk in australia: 50%
- 4x as common as all other cancers combined
- costs 1 billion anually
= continues to increase in older groups
Melanoma stats
- NSW: 1 in 20 (more common in men)
- Qld: 1 in 16: worlds highest incidence
- anually in Australia: 13000 new cases and 1600 deaths
Basal cell carcinoma
- most common skin cancer
- 50% of Australians
- Slow growing
- almost never metastasizes
- can be quite destructive
Very different types: superficial, nodular, pigmented, micronodular, infiltrating, morphoeic
Actinic keratoses
- sunspots
- > 60% of Australians over 40
- Premalignant: can progress to SCC
- may spontaneously resolbe
- tenderness may indicate progression
Squamous cell carcinoma
- 2-3x less common than BCC
- can metastasize to nodes, lungs and bone
- risk depends on site, size and differentiation and host immunity
What causes skin cancer
- DNA damage
- immunosuppression
- UV induced DNA damage or immunosuppression
Melanoma risk factors
- acute, intermittent UV exposure in childhood, adolescence and adulthood
- some increase risk with chronic UV
- immunosuppression: 5-6x fold increase
- genetic rpedisposition
- pale skin
- multiple bland or dysplastic naevi
BCC risk factor
- episodic/recreational UV
- sunburns
- immunosuppression
- Genetic: Xeroderma pigmentosum or Gorlin syndrome
Carcinogenic
- arsenic
- UV
- radiotherapy
SCC risk factor
- chronic UV exposure
- up to 80% of SCC arise from AK
- immunosuppression
- HPV is a cocarniogenic with UV
Skin cancer prevention goals
- prevent DNA damage
- protect skin immunifty
- enhance DNA repair
- replenish cellular energy
Skin cancer prevention strategies
- minimise UV exposure
- sunscreen
- chemoprevention
UV minimisation
- avoid sunburn
- sunglasses: prevent peripheral light focusing
- shade
- hats
- tightly woven clothing
Diet and skin cancer
- higher omega 3 and 6FA may lower skin cancer risk
- obesity and increase melanoma risk
- decrease SCC risk with leafy greens
Stress and skin cancer
- acute stress bumps up immunity
- chronic stress increases photocarcinogenesis
Smoking and skin cancer
- 2x risk of AK and SCC
- surgical transplants less easy
- smoking increases immunosuppression
Sunscreens
- chemical absorbers: cinnamate and oxybenzone
- physical blockers: zinc oxide, titanium dioxide
Measuring sunscreen protection from erythema: SPF
SPF = MED of sunscreen-protected skin / MED of unprotected skin
Factors affecting the SPF
- sunscreen film thickness (people put 3x less than recomended)
- substantivity
- UV spectrum: sunlight has more UVA
- skin type
- photodecay of sunscreen active agents
Rule of thumb for SPF
- real life SPF is hald the laboratory SPF
UV immunosuppression
- immunosuppression increases skin cancer risk
- even low UV doses suppress skin immunity
- UV immunosuppression plays a key role in skin cancer development
How well do sunscreens prevent immunosuppression?
- sunscreens are generally better at preventing sunburn than immunosuppression
- broad spectrum sunscreens (UVB and UVA) are more immune protective
Nanoparticles in sunscreen
- zinc and titanium
- are harmful if you inhale them
- don’t penetrate normal stratum corneum
- UV does penetrate stratum corneum
Do sunscreens prevent skin cancer?
- reduce AK/SCC risk by 40% in 2 years
- may reduce BCC and melanoma after 8 years
Other chemopreventers: Retinoids (VitA related)
- acitrecin in transplant patient
- can have liver, lipid and bone side effects
- dry skin, dry lips, hair loss, teratogenic
Other chemopreventers: COX inhibitors
- opical NSAIDS: diclofenac gel for AK
- decrease SCC in people taking aspirin/NSAIDS
- 40% reduction in BCC/SCC with celcoxib
DNA repair enhancers
- T4N5 liposomes
- decrease AK, BCC in xeroderma pigmentosum patients
Nicotinamide
- amide form of vit B3
- precursor of NAD
- deficiency can result in pellagra
- recomended daily intake: 15-20 mg/day
- more pleasant than nicotinic acid (niacin)
Pellagra symptoms:
- diarrhoea
- dementia
- dermatitis
Nicotamide effects
- UV protective in mice: prevent UV immunosuppression and photocarcinogenesis
- prevent UV immunosuppression in humans
- gives broad spectrum immune protection
How does nicotinamide work?
- may replenish cellular energy -> enhance DNA repair
- enhances cellular ATP after UV -> DNA repair
- increases repair of both direct, UVB-type damage (CPD) and oxidative (UVA) DNA damage
- enhances DNA repair after arsenic and UV
Can nicotinamide prevent skin cancer
- 29% reduction in risk in AK by 4 months
- reduced number of neu skin cancer
- reduced skin cancer by 23% in heavily sun damaged people
- nicotinamide is only in phase 2 study.
Benefits of nicotinamide
- well tolerated
- cheap
- already widely available
Nicotinamide in the clinic
- for patients who have already had multiple (non-melanoma) skin cancers)
- no evidence of efficacy in low risk people
Men and sun protection
- men are immunologically weaker
- testosterone is immune suppressive: men a re more susceptible to UV immunosuppression
- higher skin cancer incidence and mortality
Secondary prevention
- a history of skin cancer greatly enhances the risk of further skin cancers
- only 50% of ONTRAC patients have recently used sunscreen
