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How Sunlight Causes Melanoma

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Abstract

The incidence of melanoma has continued to rise dramatically over the past few decades, especially in young females. Due to the deadly nature of this disease, melanoma has become an important public health problem. It is generally accepted that ultraviolet light radiation (UVR) from sunlight is a major risk factor for melanoma skin cancer development. However, the mechanistic details of how sunlight via UVR causes melanoma are still being elucidated. Currently, it is thought that carcinogenic, inflammatory, and immunosuppressive properties of UVR all contribute to initiation, progression, and metastasis of primary melanoma. We review current findings on how sunlight-generated UVR generates DNA damage, inflammation, and immune suppression, thus leading to melanoma.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Albert MR, Ostheimer KG: The evolution of current medical and popular attitudes toward ultraviolet light exposure: part 1. J Am Acad Dermatol 2002, 47:930–937.

    Article  PubMed  Google Scholar 

  2. Young C: Solar ultraviolet radiation and skin cancer. Occup Med (Lond) 2009, 59:82–88.

    Article  Google Scholar 

  3. •• Schulman JM, Fisher DE: Indoor ultraviolet tanning and skin cancer: health risks and opportunities. Curr Opin Oncol 2009, 21:144–149. This recent review explored the role of UV radiation exposure and indoor tanning bed use in melanoma and nonmelanoma skin cancer risk, and concluded that indoor tanning bed use represents an avoidable risk factor for skin cancer. This review also analyzed in detail the benefits of vitamin D in preventing different types of cancers.

    Article  CAS  PubMed  Google Scholar 

  4. Garland CF, Garland FC, Gorham, ED, et al.: The role of vitamin D in cancer prevention. Am J Public Health 2006, 96:252–261.

    Article  PubMed  Google Scholar 

  5. Tran TT, Schulman J, Fisher DE: UV and pigmentation: molecular mechanisms and social controversies. Pigment Cell Melanoma Res 2008, 21:509–516.

    Article  CAS  PubMed  Google Scholar 

  6. Clifton V: Attorney General’s office files suit against Darque Tan for false ad claims. The Sun (online news). November 15, 2008.

  7. Armstrong BK, Kricker A: The epidemiology of UV induced skin cancer. J Photochem Photobiol 2001, 63:8–18.

    Article  CAS  Google Scholar 

  8. Whiteman DC, Whiteman CA, Green AC: Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies. Cancer Causes Control 2001, 12:69–82.

    Article  CAS  PubMed  Google Scholar 

  9. Caini S, Gandini S, Sera F, et al.: Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant. Eur J Cancer 2009, 45:3054–3063.

    Article  PubMed  Google Scholar 

  10. •• Cui R, Widlund HR, Feige E, et al.: Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 2007, 128:853–864. This study provided a molecular mechanism by which UV exposure causes tanning via p53 activation. It showed that p53 is activated in response to DNA damage, suggesting that UV-mediated tanning likely occurs secondary to DNA damage and thus carries the risk of carcinogenesis and cancer development.

    Article  CAS  PubMed  Google Scholar 

  11. Valverde P, Healy E, Jackson I, et al.: Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet 1995, 11:328–330.

    Article  CAS  PubMed  Google Scholar 

  12. Karagas MR, Stannard VA, Mott LA, et al.: Use of tanning devices and risk of basal cell and squamous cell skin cancers. J Natl Cancer Inst 2002, 94:224–226.

    PubMed  Google Scholar 

  13. Ting W, Schultz K, Cac NN, et al.: Tanning bed exposure increases the risk of malignant melanoma. Int J Dermatol 2007, 46:1253–1257.

    PubMed  Google Scholar 

  14. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: A systematic review. Int J Cancer 2007, 120:1116–1122.

  15. Lazovich D, Berwick M, Weinstock MA, et al.: Indoor tanning and risk of melanoma: a case-control study in a highly exposed population. Cancer Epidemiol Biomarkers Prev 2010, In Press.

  16. •• Purdue MP, Freeman LE, Anderson WF, Tucker MA: Recent trends in incidence of cutaneous melanoma among US Caucasian young adults. J Invest Dermatol 2008, 128:2905–2908. This recent study showed a dramatic rise in incidence of melanoma in young females. Most alarmingly, this study also demonstrated a striking increase in incidence of regionally and distantly spread disease in young females. The authors suggested that this increase in incidence of melanoma in young females could be from their increased UVR exposure through the use of tanning beds.

    Article  CAS  PubMed  Google Scholar 

  17. Curtin JA, Fridlyand J, Kageshita T, et al.: Distinct sets of genetic alterations in melanoma. N Engl J Med 2005, 353:2135–2147.

    Article  CAS  PubMed  Google Scholar 

  18. Diepgen TL, Mahler V: The epidemiology of skin cancer. Br J Dermatol 2002, 146(Suppl 61):1–6.

    Article  PubMed  Google Scholar 

  19. Gandini S, Sera F, Cattaruzza MS, et al.: Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer 2005, 41:45–60.

    Google Scholar 

  20. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S: Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Ann Rev Biochem 2004, 73:39–85.

    Article  CAS  PubMed  Google Scholar 

  21. Roos WP, Kaina B: DNA damage-induced cell death by apoptosis. Trends Mol Med 2006, 12:440–450.

    Article  CAS  PubMed  Google Scholar 

  22. Ziegler A, Jonason AS, Leffell DJ, et al.: Sunburn and p53 in the onset of skin cancer. Nature 1994, 372:773–776.

    Article  CAS  PubMed  Google Scholar 

  23. Jonason AS, Kunala S, Price GJ, et al.: Frequent clones of p53-mutated keratinocytes in normal human skin. Proc Natl Acad Sci U S A 1996, 93:14025–14029.

    Article  CAS  PubMed  Google Scholar 

  24. •• IARC: IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Lyon, France: International Agency for Research on Cancer; Volume 55: 1992. This large meta-analysis provided extensive evidence to confirm the association between indoor tanning and melanoma. It also showed that first exposure to indoor tanning before age 35 was associated with 75% increased risk of developing melanoma.

  25. Clingen PH, Arlett CF, Roza L, et al.: Induction of cyclobutane pyrimidine dimers, pyrimidine(6-4)pyrimidone photoproducts, and Dewar valence isomers by natural sunlight in normal human mononuclear cells. Cancer Res 1995, 55:2245–2248.

    CAS  PubMed  Google Scholar 

  26. Ravanat JL, Douki T, Cadet J: Direct and indirect effects of UV radiation on DNA and its components. J Photochem Photobiol 2001, 63:88–102.

    Article  CAS  Google Scholar 

  27. Cadet J, Sage E, Douki T: Ultraviolet radiation-mediated damage to cellular DNA. Mutat Res 2005, 571:3–17.

    CAS  PubMed  Google Scholar 

  28. Agar NS, Halliday GM, Barnetson RS, et al.: The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc Natl Acad Sci U S A 2004, 101:4954–4959.

    Article  CAS  PubMed  Google Scholar 

  29. Garland CF, Garland FC, Gorham ED: Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates. Ann Epidemiol 2003, 13:395–404.

    Article  PubMed  Google Scholar 

  30. • Besaratinia A, Pfeifer GP: Sunlight ultraviolet irradiation and BRAF V600 mutagenesis in human melanoma. Hum Mutat 2008, 29:983–991. This review article discussed the use of “DNA damage-targeted mutagenicity” of UVR for determining the mechanistic involvement of sunlight in specific gene mutagenesis in human melanoma. By analyzing specific DNA lesions found in BRAF gene from melanomas, they explained how UVR could be the culprit of BRAF mutagenesis.

    Article  CAS  PubMed  Google Scholar 

  31. Besaratinia A, Pfeifer GP: Investigating human cancer etiology by DNA lesion footprinting and mutagenicity analysis. Carcinogenesis 2006, 27:1526–1537.

    Article  CAS  PubMed  Google Scholar 

  32. Mouret S, Baudouin C, Charveron M, et al.: Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proc Natl Acad Sci U S A 2006, 103:13765–13770.

    Article  CAS  PubMed  Google Scholar 

  33. Wang Y, Digiovanna JJ, Stern JB, et al.: Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas. Proc Natl Acad Sci U S A 2009, 106:6279–6284.

    Article  CAS  PubMed  Google Scholar 

  34. English JS, Swerdlow AJ: The risk of malignant melanoma, internal malignancy and mortality in xeroderma pigmentosum patients. Br J Dermatol 1987, 117:457–461.

    Article  CAS  PubMed  Google Scholar 

  35. Daya-Grosjean L, Sarasin A: The role of UV induced lesions in skin carcinogenesis: an overview of oncogene and tumor suppressor gene modifications in xeroderma pigmentosum skin tumors. Mut Res 2005, 571:43–56.

    CAS  Google Scholar 

  36. Kuphal S, Bosserhoff A: Recent progress in understanding the pathology of malignant melanoma. J Pathol 2009, 219:400–409.

    Article  CAS  PubMed  Google Scholar 

  37. Williams M, Ouhtit A: Towards a better understanding of the molecular mechanisms involved in sunlight-induced melanoma. J Biomed Biotechnol 2005, 57–61.

  38. Pleasance ED, Cheetham RK, Stephens PJ, et al.: A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010, 463:191–196.

    Article  CAS  PubMed  Google Scholar 

  39. Maddodi N, Setaluri V: Role of UV in cutaneous melanoma. Photochem Photobiol 2008, 84:528–536.

    Article  CAS  PubMed  Google Scholar 

  40. Davies H, Bignell GR, Cox C, et al.: Mutations of the BRAF gene in human cancer. Nature 2002, 417:949–954.

    Article  CAS  PubMed  Google Scholar 

  41. Pollock PM, Harper UL, Hansen KS, et al.: High frequency of BRAF mutations in nevi. Nat Genet 2003, 33:19–20.

    Article  CAS  PubMed  Google Scholar 

  42. Thomas NE, Alexander A, Edmiston SN, et al.: Tandem BRAF mutations in primary invasive melanomas. J Invest Dermatol 2004, 122:1245–1250.

    Article  CAS  PubMed  Google Scholar 

  43. • Thomas NE, Edmiston SN, Alexander A, et al.: Number of nevi and early-life ambient UV exposure are associated with BRAF-mutant melanoma. Cancer Epidemiol Biomarkers Prev 2007, 16:991–997. This population-based case series study showed association of BRAF mutations with early-life UV exposure. The results highlighted the importance of childhood sun protection for melanoma prevention.

    Article  CAS  PubMed  Google Scholar 

  44. Edwards RH, Ward MR, Wu H, et al.: Absence of BRAF mutations in UV-protected mucosal melanomas. J Med Genet 2004, 41:270–272.

    Article  CAS  PubMed  Google Scholar 

  45. Schwarz T: 25 years of UV-induced immunosuppression mediated by T cells—from disregarded T suppressor cells to highly respected regulatory T cells. Photochem Photobiol 2008, 84:10–18.

    Article  CAS  PubMed  Google Scholar 

  46. Murphy GM: Ultraviolet radiation and immunosuppression. Br J Dermatol 2009, 161(Suppl 3):90–95.

    Article  CAS  PubMed  Google Scholar 

  47. Penn I: Post-transplant malignancy: the role of immunosuppression. Drug Saf 2000, 23:101–113.

    Article  CAS  PubMed  Google Scholar 

  48. Euvrard S, Kanitakis J, Claudy A: Skin cancers after organ transplantation. N Engl J Med 2003, 348:1681–1691.

    Article  PubMed  Google Scholar 

  49. Mantovani A: Cancer: inflammation by remote control. Nature 2005, 435:752–753.

    CAS  Google Scholar 

  50. Coussens LM, Werb Z: Inflammation and cancer. Nature 2002, 420:860–867.

    Article  CAS  PubMed  Google Scholar 

  51. Halliday GM: Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mut Res 2005, 571:107–120.

    CAS  Google Scholar 

  52. Stafforini DM, McIntyre TM, Zimmerman GA, Prescott SM: Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Crit Rev Clin Lab Sci 2003, 40:643–672.

    Article  CAS  PubMed  Google Scholar 

  53. Melnikova V, Bar-Eli M: Inflammation and melanoma growth and metastasis: the role of platelet-activating factor (PAF) and its receptor. Cancer Metastasis Rev 2007, 26:359–371.

    Article  CAS  PubMed  Google Scholar 

  54. Ullrich SE: Sunlight and skin cancer: lessons from the immune system. Mol Carcinog 2007, 46:629–633.

    Article  CAS  PubMed  Google Scholar 

  55. McCarter M, Clarke J, Richter D, Wilson C: Melanoma skews dendritic cells to facilitate a T helper 2 profile. Surgery 2005, 138:321–328.

    Article  PubMed  Google Scholar 

  56. Rankin EB, Yu D, Jiang J, et al.: An essential role of Th1 responses and interferon gamma in infection-mediated suppression of neoplastic growth. Cancer Biol Ther 2003, 2:687–693.

    CAS  PubMed  Google Scholar 

  57. Clement-Lacroix P, Michel L, Moysan A, et al.: UVA-induced immune suppression in human skin: protective effect of vitamin E in human epidermal cells in vitro. Br J Dermatol 1996, 134:77–84.

    Article  CAS  PubMed  Google Scholar 

  58. Stene MA, Babajanians M, Bhuta S, Cochran AJ: Quantitative alterations in cutaneous Langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol 1988, 91:125–128.

    Article  CAS  PubMed  Google Scholar 

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Garibyan, L., Fisher, D.E. How Sunlight Causes Melanoma. Curr Oncol Rep 12, 319–326 (2010). https://doi.org/10.1007/s11912-010-0119-y

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