AHS13 Anastasia Boulais — Is Sun Worshipping Increasing Your Risk of Melanoma?

IS SUN WORSHIPPING INCREASING YOUR RISK OF MELANOMA?

Dr Anastasia BoulaisAncestral Health Symposium

Atlanta 2013

FAT MAKES YOU FAT

Dr Anastasia Boulais AHS13

FAIL!


BUTTER CAUSES HEART ATTACKS


FAIL!

THE EVIL ORB IN THE SKY IS OUT TO GIVE YOU LETHAL CANCER


FAIL?


Australia: World Leader in Melanoma

• CMM – cutaneous malignant melanoma (not “skin cancer”)• Highest incidence in the world• 10% of all cancers• 1 in 17 Australians will develop melanoma before the age of

85• 3.4% of all cancer deaths in 2010• 1980 – “Slip, slop, slap” campaign• 1986-2006 – Melanoma rates double

PRO AGAINST

1. Known cellular mechanism 1. Lower incidence in outdoor workers vs. indoor workers

2. Increased incidence with latitude 2. CMM more prevalent on less sun-exposed sites

3. Increased incidence in sunbed use 3. Negative correlation between chronic exposure and incidence of CMM

4. Association with sunburns 4. Vitamin D inhibits growth of tumours

5. Sun exposure > atypical naevi > strong risk factor for melanoma

5. Increased melanoma survival with higher sun exposure history

6. Sunscreens have not been found to decrease CMM incidence


Does sunlight cause melanoma?

Does food cause heart disease?


ultraviolet

visible

UVA

UVB

UVC

UVA UVB

UVC

ozone


UVA SKIN PENETRATION

• UVA – longer wavelength with deeper skin penetration.

• Low erythema potential• Not absorbed by ozone layer• Immediate & Persistent

Pigment Darkening (IPD/PPD)• UVA tan via oxidation of

melanin precursors in basal cell layer, not an increase in melanin content.


UVA RADIATION

• Indirect DNA damage via formation of ROS oxidative stress• No significant photoprotection• Breaks down Vitamin D bound to VDR• Induces NO¯ formation• Inhibits UVB-induced immunosuppression


- PROTEIN DAMAGE - LIPID DAMAGE - DNA DAMAGE

Sunbeds give off 5-10x more UVA than experienced at solar noon in Southern Europe


UVB SKIN PENETRATION

• UVB – poor skin penetration.• High erythema [burn] potential• Partially absorbed by ozone

layer• Delayed tanning (DT) 3-7 days

post exposure lasts for weeks• UVB tan via increased

synthesis of melanin and increased melanocyte density


UVB RADIATION

• Direct DNA damage via formation of cyclobutane pyrimidine dimers [CPD] and 6-4 photoproducts [6-4PP]

• Delayed tan = photoprotection• Skin adaptations: hyperkeratosis and thickening of stratum

corneum• Vitamin D production

Source: Lester M.Davids “Recent Advances in the Biology, Therapy and Management of Melanoma” Published Feb 2013 under CC BY3.0 license


Irradiation

Solar Zenith Angle (the

shadow rule)

Latitude

Time of the year

Time of dayElevation

Ozone concentration

UVB PARTIAL OZONE ABSORPTION

Las Cruces , NM32.6° north latitudeJune 21Clear dayMiddayCurrent ozone level

Seattle, WA47.7° north latitudeJune 21Clear dayMiddayCurrent ozone level

1.24x more UVB

Source: http://uvb.nrel.colostate.edu/UVB/publications/uvb_primer.pdf

MELANOMA ACTION SPECTRUM?

“…the available evidence points away from pyrimidine dimer formation by UVB and toward oxidative damage caused by longer [UVA] wavelengths.”

Lund et al (2007) Melanoma, long wavelength ultraviolet and sunscreens: Controversies and potential resolutions , Pharmacology and Therapeutics

UVA UVB

INDIRECT DNA DAMAGE

DIRECT DNA DAMAGE


INNATE PROTECTION AND REPAIR

1. Delayed Tanning photon absorption2. Skin adaptation3. Melatonergic Antioxidant System4. Nucleotide Excision Repair 5. Endogenous + exogenous ROS quenchers6. Vitamin D – potent immunomodulator


MELATONERGIC ANTIOXIDANT SYSTEM

• Melatonin is produced in pineal gland, bile fluid, BM, CSF, ovary, eyes, lymphocytes, gastric mucosa and skin

• Antioxidant – strong scavenger of UV-induced ROS

• Modulates UV-induced apoptosis• Tumour growth inhibitor


NUCLEOTIDE EXCISION REPAIR

• XPA [Xeroderma Pigmentosum Group A]– A critical protein involved in DNA damage recognition

• XPA is a rate-limiting factor in excision repair controlled by a circadian clock

• In [nocturnal] mice: CPD + 6-4PP repaired faster in 4pm group (XPA zenith) vs. 4am group (XPA nadir)

• In humans this peak repair rate would coincide with the morning hours up to around solar noon.


CIRCADIAN RHYTHM FTW!

INCREASED UVA TO UVB RATIO

↓ erythema↑ oxidative stress↓ melanin production↓ Vitamin D production↑ Vitamin D breakdown↓ protective skin adaptation

A tan with no photoprotection


EXOGENOUS ANTIOXIDANTS AND PRO-OXIDANTS

Antioxidants• Carotenoids

– Beta-carotene– Lutein– Lycopene

• Flavonoids and Polyphenols– Tea and cocoa polyphenols– Herbs and spices

• Ascorbic acid• Vitamin E (tocopherols)

Pro-oxidants• Increased risk with high PUFA diet (RR 2-4), high

linoleic acid (RR 2.16) and cod liver oil (RR 2.9)• Recall: Sunbed RR 1.2

In vitro studiesEpidemiological evidenceHuman RCTs (erythema)


PHYSIOLOGICAL STRESS?

• Increased number of atypical naevi in marathon runners• Training HR, training velocity and physical strain index

• Cortisol? • Oxidative stress?• Impaired carcinogenesis repair?


THERE’S NOTHING HEALTHY ABOUT A TAN?

HIGH INTAKE OF PRO-OXIDANTS

LOW VITAMIN D STATUS

PHYSIOLOGICAL STRESS

CIRCADIAN RHYTHM DYSRUPTION

POOR INTAKE OF ANTIOXIDANTS

HIGH UVA/UVB RATIO

GENETICS MELANOMA RISK

Know your risk…

Eat wellSleep better

Enjoy movementManage your stressSmart sun exposure

BIBLIOGRAPHY1. Juzeniene A, Moan J (2012) Beneficial effects of UV radiation other than via vitamin D production. Dermato-Endocrinology, 4:2, 109-

1172. Desotelle J, Wiling M, Ahmad N (2012) The Circadian Control of Skin and Cutaneous Photodamage. Photochemistry and Photobiology,

88: 1037-10473. Boniol M, Autier P, Boyle P, Gandini S (2012) Cutaneous melanoma attributable to sunbed use: systemic review and meta-analysis.

BMJ 345: e47574. Gaddameedhi S, Selby C, Kaufmann W, Smart R, Sancar A (2011) Control of skin cancer by the circadian rhythm. PNAS Online5. Weinstock M (1996) Controversies in the role of sunlight in the pathogenesis of CM . Photochemistry and Photobiology 63(4)6. Vinceti M, Pellacani G, Malagoli C, Bassissi S, Sieri S, Bonvicini F, Krogh V, Seidenari S (2005) A population-based case-control study of

diet and melanoma risk in Northern Italy. Public Health Nutrition 8(8) 1307-13147. Veierod M, Helle D, Aake P (1997) Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and

women. Int. J Cancer: 71, 600-6048. De Giorgi V, Gori A, Grazzini M, Rossari A, Oranges T, Longo A, Lotti T, Gandini S (2012) Epidemiology of melanoma: is it still

epidemic? What is the role of the sun, sunbeds, Vit D, betablocks, and others? Dermatologic Therapy, 25: 392-3969. Godar D, Landry R, Lucas A (2009) Increased UVA exposures and decreased cutaneous Vitamin D3 levels may be responsible for the

increasing incidence of melanoma. Medical Hypothesis, 72:434-44310. Richtig E, Ambros-Rudolph C, Trapp M, Lackner H, Hofmann-Wellenhof R, Kerl H, Schwaberger G (2008) Melanoma markers in

marathon runners: increase with sun exposure and physical strain. Dermatology 217:38-4411. Lund C, Timmins G (2007) Melanoma, long wavelength ultraviolet and sunscreens: controversies and potential resolutions.

Pharmacology and Therapeutics, 114: 198-20712. Shapira N (2010) Nutritional approach to sun protection: a suggested complement to external strategies. Nutrition Review, 68(2) 71-

8613. Rosso S, Sera F, Segnan N, Zanetti R (2008) Sun exposure prior to diagnosis is associated with improved survival in melanoma patients:

Results from a long-term follow-up study of Italian patients. European Journal of Cancer, 44: 1275-128114. Agar N, Halliday G, Barnetson R, Ananthaswamy H, Wheeler M, Jones A (2004) The basal layer in human squamous tumors harbors

more UVA than UVB fingerprint mutations: A role for UVA in human skin carcinogenesis. PNAS 101(14): 4954-495915. Miyamura Y, Coelho S, Schlenz K, Batzer J, Smuda C, Choi W, Brenner M, Passeron T, Zhang G, Kolbe L, Wolber R, Hearing V (2011) The

deceptive nature of UVA-tanning versus the modest protective effects of UVB-tanning on human skin. Pigment Cell Melanoma Res 24(1); 136-147


AHS13 Anastasia Boulais — Is Sun Worshipping Increasing Your Risk of Melanoma?

Health & Medicine

Transcript of AHS13 Anastasia Boulais — Is Sun Worshipping Increasing Your Risk of Melanoma?