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Genetic epidemiology of melanoma

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European Journal of Dermatology

Abstract

The field of melanoma genetics is moving at great pace with new platforms to investigate single nucleotide polymorphism, genome sequencing, gene expression, and methylation. Melanoma incidence is still rising mainly because of screening campaigns, which has increased the number of reported melanomas.However, mortality due to melanoma is not decreasing. Many cutaneous phenotypic risk factors have been linked to melanoma, but the association with UV radiation is very complex. The level of vitamin D affects both the risk of melanoma and prognosis, but more studies are needed. The genetics of melanoma involves genes involved in pigmentation and naevi, as well as genes involved in the cell cycle and senescence, which have been identified via genome-wide association studies over the last 10 years. One area of research highly relevant to melanoma is telomere biology with further links to reduced senescence. At the somatic level, new gene pathways are being explored with many new therapeutic targets, and boosting immune responses against the tumour appears to offer the best long-term outcome.

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References

  1. Gershenwald JE, Guy GP Jr.. Stemming the rising incidence of melanoma: calling prevention to action. J Natl Cancer Inst 2015; 12: 108.

    Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. Whiteman DC, Brown RM, Purdie DM, Hughes MC. Prevalence and anatomical distribution of naevi in young Queensland children. Int J Cancer 2003; 106: 930–3.

    Article  CAS  PubMed  Google Scholar 

  4. Bataille V, Sasieni P, Grulich A, et al. Solar keratoses: a risk factor for melanoma but negative association with melanocytic naevi. Int J Cancer 1998; 78: 8–12.

    Article  CAS  PubMed  Google Scholar 

  5. de Vries E, Coebergh JW. Cutaneous malignant melanoma in Europe. Eur J Cancer 2004; 40: 2355–66.

    Article  PubMed  Google Scholar 

  6. Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst 2010; 102: 605–13.

    Article  PubMed  Google Scholar 

  7. Coory M, Baade P, Aitken J, et al. Trends in situ and invasive melanoma in Queensland, Australia 1982-2002. Cancer Causes Control 2006; 17: 21–2.

    Article  PubMed  Google Scholar 

  8. Weyers W. The “epidemic” of melanoma between under and overdiagnosis. J Cutan Pathol 2012; 39: 9–16.

    Article  PubMed  Google Scholar 

  9. Sitas F, Gibberd A, Khan C, et al. Cancer incidence and mortality in people aged less than 75 years: changes in Australia over the period 1987-2007. Cancer Epidemiol 2013; 37: 780–7.

    Article  PubMed  Google Scholar 

  10. Ribero S, Osella-Abate S, Sanlorenzo M, et al. Sentinel lymph node biopsy in thick-melanoma patients (n = 350): what is its prognostic role? Ann Surg Oncol 2015; 22: 1967–73.

    Article  CAS  PubMed  Google Scholar 

  11. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/skin/incidence/uk-skin-cancer-incidence-statistics).

  12. Field S, Davies J, Bishop DT, Newton-Bishop JA. Vitamin D and melanoma. Dermatoendocrinol 2013; 5: 121–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ribero S, Zugna D, Osella-Abate S, et al. Prediction of high naevus count in a healthy UK population to estimate melanoma risk. Br J Dermatol 2015; 219: 530.

    Google Scholar 

  14. Goldstein AM, Chan M, Harland M, et al. High risk melanoma susceptibility genes and pancreatic cancer, neural system tumors and uveal melanomas across GenoMEL. Cancer Res 2006; 15: 9818–28.

    Article  Google Scholar 

  15. Bataille V. Sun exposure, sunbeds and sunscreens and melanoma. What are the controversies? Curr Oncol Rep 2013; 15: 526–32.

    Article  PubMed  Google Scholar 

  16. Whiteman DC, Whiteman AC, 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 

  17. Bulliard JL. Site specific risk of cutaneous malignant melanoma and pattern of sun exposure in New Zealand. Int J Cancer 2000; 85: 627–32.

    Article  CAS  PubMed  Google Scholar 

  18. Lens MB, Dawes M. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br J Dermatol 2004; 150: 179–85.

    Article  CAS  PubMed  Google Scholar 

  19. Nelemans PJ, Rampen FH, Ruiter DJ, Verbeek AL. An addition to the controversy on sunlight exposure and melanoma risk: a metaanalytical approach. J Clin Epidemiol 1995; 48: 1331–42.

    Article  CAS  PubMed  Google Scholar 

  20. Veierød MB, Parr CL, Lund E, Hjartåker A. Reproducibility of selfreported melanoma risk factors in a large cohort study of Norwegian women. Melanoma Res 2008; 18: 1–9.

    Article  PubMed  Google Scholar 

  21. Chang YM, Barrett JH, Bishop DT, et al. Sun exposure and melanoma risk at different latitudes: a pooled analysis of 5700 cases and 7216 controls. Int J Epidemiol 2009; 38: 814–30.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Darlington S, Williams G, Nearle R, Frost C, Green A. A randomize controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses. Arch Dermatol 2003; 139: 451–5.

    Article  PubMed  Google Scholar 

  23. Friedman B, English JC 3rd., Ferris LK. Indoor tanning, skin cancer and the young female patient: a review of the literature. J Pediatr Adolesc Gynecol 2015; 28: 275–8.

    Article  PubMed  Google Scholar 

  24. Boniol M, Autier P, Boyle P, Gandini S. Cutaneous melanoma attribuitable to sunbed use: systematic review and meta-analysis. BMJ 2012; 345: e4757.

    Article  Google Scholar 

  25. Nilsen LT, Hannevik M, Veierød MB. UV exposure from indoor tanning devices: a systematic review. Br J Dermatol 2016. In press.

    Google Scholar 

  26. Katalinic A, Waldmann A, Weinstock MA, et al. Does skin cancer screening save Lives? An observational study comparing trends in melanoma mortality in regions with and without screening. Cancer 2012; 118: 5395–402.

    Article  PubMed  Google Scholar 

  27. Field S, Davies J, Bishop DT, Newton-Bishop JA. Vitamin D and melanoma. Dermatoendocrinol 2013; 5: 121–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fleet JC, DeSmet M, Johnson R, Li Y, Vitamin D. cancer: a review of molecular mechanisms. Biochem J 2012; 441: 61–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Davies JR, Chang YM, Snowden H, et al. The determinants of serum vitamin D levels in participants in a melanoma case-control study living in a temperate climate. Cancer Causes Control 2011; 22: 1471–82.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Glass D, Lens M, Swaminathan R, Spector TD, Bataille V. Pigmentation and vitamin D metabolism in Caucasians: low vitamin D serum levels in fair skin types in the UK. PLoS One 2009; 4: e6477.

    Article  Google Scholar 

  31. Saiag P, Aegerterm P, Vitoux D, et al. Prognostic value of 25-hydroxyvitamin D3 levels at diagnosis and during follow-up in melanoma patients. J Natl Cancer Inst 2015; 107: djv264.

    Article  PubMed  Google Scholar 

  32. Puig S, Malvehy J. Monitoring patients with multiple nevi. Dermatol Clin 2013; 31: 565–77.

    Article  CAS  PubMed  Google Scholar 

  33. Marzuka-Alcala A, Gabree MJ, Tsao H. Melanoma susceptibility genes and risk assessment. Methods Mol Biol 2014; 1102: 381–93.

    Article  CAS  PubMed  Google Scholar 

  34. Read J, Wadt KA, Hayward NK. Melanoma genetics. J Med Genet 2016; 53: 1–14.

    Article  CAS  PubMed  Google Scholar 

  35. Bohm M, Schiller M, Luger TA. Non-pigmentary actions of alpha-melanocyte-stimulating hormone-lessons from the cutaneous melanocortin system. Cell Mol Biol 2006; 30: 61–8.

    Google Scholar 

  36. Tomiyama H, Yoshino H, Ogaki K, et al. PLA2G6 variant in Parkinson disease. J Hum Genet 2011; 56: 401–3.

    Article  CAS  PubMed  Google Scholar 

  37. Ogbah Z, Badenas C, Harland M, et al. Evaluation of PAX3 genetic variants and nevus number. Pigment Cell Melanoma Res 2013; 26: 666–76.

    Article  CAS  PubMed  Google Scholar 

  38. Bataille V, Kato BS, Falchi M, et al. Nevus size and number are associated with telomere length and represent potential markers of a decreased senescence in vivo. Cancer Epidemiol Biomarkers Prev 2007; 16: 1499–502.

    Article  CAS  PubMed  Google Scholar 

  39. Ribero S, Glass D, Aviv A, Spector TD, Bataille V. Height and bone mineral density are associated with naevus count supporting the importance of growth in melanoma susceptibility. PLoS One 2015; 10: e0116863.

    Article  Google Scholar 

  40. Bodelon C, Pfeiffer RM, Bollati V, et al. On the interplay of telomeres, nevi and risk of melanoma. Plos One 2012; 7: e52466.

    Article  Google Scholar 

  41. Han J, Qureshi AA, Prescott J, et al. A prospective study of telomere length and the risk of skin cancer. J Invest Dermatol 2009; 129: 415–21.

    Article  CAS  PubMed  Google Scholar 

  42. Nan H, Du M, De Vivo I, et al. Shorter telomeres associate with a reduced risk of melanoma development. Cancer Res 2011; 71: 6758–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Iles MM, Bishop DT, Taylor JC, et al. The effect on melanoma risk of genes previously associated with telomere length. J Natl Cancer Inst 2014, 106 pii: dju267.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Huang FW, Hodis E, Xu MJ, et al. Highly recurrent TERT promoter mutations in human melanoma. Science 2013; 6122: 957–9.

    Article  Google Scholar 

  45. Peeper DS. Oncogene-induced senescence and melanoma. Where do we stand? Pigment Cell Melanoma Res 2011; 24: 1107–11.

    Article  PubMed  Google Scholar 

  46. Mann GJ, Pupo GM, Campain AE, et al. BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in patients with stage III melanoma. J Invest Dermatol 2013; 133: 509–17.

    Article  CAS  PubMed  Google Scholar 

  47. Wangari-Talbot J, Chen S. Genetics of melanoma. Front Genet 2013; 3: 330.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Berger MF, Hodis E, Heffernan TP, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 2012; 485: 502–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Turajlic S, Furney SJ, Lambros MB, et al. Whole genome sequencing of matched primary and metastatic acral melanomas. Genome Res 2012; 22: 196–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Berger MF, Hodis E, Heffernan TP, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 2012; 485: 502–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Furney SJ, Turajlic S, Stamp G, et al. Genome sequencing of mucosal melanomas reveal that they are driven by distinct mechanisms from cutaneous melanoma. J Pathol 2013; 230: 261–9.

    Article  CAS  Google Scholar 

  52. Boussiotis VA. Somatic mutations and immunotherapy outcome with CTLA-4 blockade in melanoma. N Engl J Med 2014; 371: 2230–2.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014; 371: 2189–99.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kreiter S, Vormehr M, van de Roemer N, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 2015; 520(7549): 692–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Greenman C, Wooster R, Futreal PA, Stratton MR, Easton DF. Statistical analysis of pathogenicity of somatic mutations in cancer. Genetics 2006; 173: 2187–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Simone Ribero.

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Ribero, S., Glass, D. & Bataille, V. Genetic epidemiology of melanoma. Eur J Dermatol 26, 335–339 (2016). https://doi.org/10.1684/ejd.2016.2787

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