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

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Those of us familiar with the evolutionary medicine model have come to question many of the conventional public health recommendations and, along with them, the complete sun avoidance. Dr Anastasia Boulais will describe the delicate balance between the benefits and risks of sun worshipping based on current evidence. The talk will focus on particular patterns of sun exposure which may increase the risk of formation of cutaneous melanoma. Other factors, such as diet, vitamin D status and even training patterns, contributing to that risk will be discussed. Anastasia will conclude with an overview of protective lifestyle factors.

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

  1. 1. IS SUN WORSHIPPING INCREASING YOUR RISK OF MELANOMA? Dr Anastasia Boulais Ancestral Health Symposium Atlanta 2013
  2. 2. FAT MAKES YOU FAT
  3. 3. FAIL! Dr Anastasia Boulais AHS13
  4. 4. BUTTER CAUSES HEART ATTACKS Dr Anastasia Boulais AHS13
  5. 5. FAIL! Dr Anastasia Boulais AHS13
  6. 6. THE EVIL ORB IN THE SKY IS OUT TO GIVE YOU LETHAL CANCER
  7. 7. FAIL? Dr Anastasia Boulais AHS13
  8. 8. 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 Dr Anastasia Boulais AHS13
  9. 9. 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
  10. 10. Does sunlight cause melanoma? Does food cause heart disease? Dr Anastasia Boulais AHS13
  11. 11. ultraviolet visible UVA UVB UVC UVA UVB UVC ozone Dr Anastasia Boulais AHS13
  12. 12. 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. Dr Anastasia Boulais AHS13
  13. 13. 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 Dr Anastasia Boulais AHS13
  14. 14. Dr Anastasia Boulais AHS13 - PROTEIN DAMAGE - LIPID DAMAGE - DNA DAMAGE
  15. 15. Sunbeds give off 5-10x more UVA than experienced at solar noon in Southern Europe
  16. 16. 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 Dr Anastasia Boulais AHS13
  17. 17. 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 Dr Anastasia Boulais AHS13
  18. 18. Source: Lester M.Davids “Recent Advances in the Biology, Therapy and Management of Melanoma” Published Feb 2013 under CC BY3.0 license
  19. 19. Irradiation Solar Zenith Angle (the shadow rule) Latitude Time of the year Time of dayElevation Ozone concentration Dr Anastasia Boulais AHS13
  20. 20. UVB PARTIAL OZONE ABSORPTION Las Cruces , NM 32.6° north latitude June 21 Clear day Midday Current ozone level Seattle, WA 47.7° north latitude June 21 Clear day Midday Current ozone level 1.24x more UVB Source: http://uvb.nrel.colostate.edu/UVB/publications/uvb_primer.pdf
  21. 21. 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
  22. 22. INNATE PROTECTION AND REPAIR 1. Delayed Tanning photon absorption 2. Skin adaptation 3. Melatonergic Antioxidant System 4. Nucleotide Excision Repair 5. Endogenous + exogenous ROS quenchers 6. Vitamin D – potent immunomodulator Dr Anastasia Boulais AHS13
  23. 23. 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 Dr Anastasia Boulais AHS13
  24. 24. 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. Dr Anastasia Boulais AHS13
  25. 25. CIRCADIAN RHYTHM FTW! Dr Anastasia Boulais AHS13
  26. 26. INCREASED UVA TO UVB RATIO ↓ erythema ↑ oxidative stress ↓ melanin production ↓ Vitamin D production ↑ Vitamin D breakdown ↓ protective skin adaptation A tan with no photoprotection
  27. 27. 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 studies Epidemiological evidence Human RCTs (erythema) Dr Anastasia Boulais AHS13
  28. 28. PHYSIOLOGICAL STRESS? • Increased number of atypical naevi in marathon runners • Training HR, training velocity and physical strain index • Cortisol? • Oxidative stress? • Impaired carcinogenesis repair? Dr Anastasia Boulais AHS13
  29. 29. Dr Anastasia Boulais AHS13
  30. 30. Dr Anastasia Boulais AHS13 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
  31. 31. Know your risk… Eat well Sleep better Enjoy movement Manage your stress Smart sun exposure
  32. 32. BIBLIOGRAPHY 1. Juzeniene A, Moan J (2012) Beneficial effects of UV radiation other than via vitamin D production. Dermato-Endocrinology, 4:2, 109-117 2. Desotelle J, Wiling M, Ahmad N (2012) The Circadian Control of Skin and Cutaneous Photodamage. Photochemistry and Photobiology, 88: 1037-1047 3. Boniol M, Autier P, Boyle P, Gandini S (2012) Cutaneous melanoma attributable to sunbed use: systemic review and meta- analysis. BMJ 345: e4757 4. Gaddameedhi S, Selby C, Kaufmann W, Smart R, Sancar A (2011) Control of skin cancer by the circadian rhythm. PNAS Online 5. 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) 1307-1314 7. 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, 600-604 8. 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: 392-396 9. 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, 72:434-443 10. 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 217:38-44 11. Lund C, Timmins G (2007) Melanoma, long wavelength ultraviolet and sunscreens: controversies and potential resolutions. Pharmacology and Therapeutics, 114: 198-207 12. Shapira N (2010) Nutritional approach to sun protection: a suggested complement to external strategies. Nutrition Review, 68(2) 71-86 13. 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- 1281 14. 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): 4954-4959 15. 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 Dr Anastasia Boulais AHS13

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