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Prevention of Skin Cancer pp 117–139Cite as

The role of genetics in the prevention of skin cancer

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Part of the book series: Cancer Prevention — Cancer Causes ((CPCC,volume 3))

Abstract

Cancer results from a complex interaction of environmental and genetic factors that impact upon a target cell, eventually leading to uncontrolled growth, invasion of adjacent structures and metastatic dissemination. Recent advances in understanding the mechanisms of carcinogenesis have emphasized the role of molecular pathways leading to cancer, raising expectations among clinicians and the public that many of today’s common afflictions will be prevented or definitively treated in the future. This chapter seeks to integrate the findings from the molecular and epidemiological paradigms, and in so doing, highlight salient issues of relevance to the control of skin cancer.

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References

  1. Harris CC (1996) p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology, and cancer risk assessment. Environ Health Perspect 104: Suppl 3:435–439.

    Google Scholar 

  2. Pitot HC (1993) The molecular biology of carcinogenesis. Cancer 72: 962–970.

    Article  PubMed  CAS  Google Scholar 

  3. Kolodner RD (2000) DNA repair: guarding against mutation. Nature 407: 607–609.

    Article  Google Scholar 

  4. Petty EM, Gibson LH, Fountain JW, et al (1993) Molecular definition of a chromosome 9p21 germ-line deletion in a woman with multiple melanomas and a plexiformneurofibroma: implications for 9p tumor-suppressor gene(s). Am J Hum Genet 53: 96–104.

    PubMed  CAS  Google Scholar 

  5. Cannon-Albright LA, Goldgar DE, Meyer LJ, et al (1992) Assignment of a locus for familial melanoma,MLM, to chromosome 9p13-p22. Science 258: 1148–1152.

    Article  PubMed  CAS  Google Scholar 

  6. Nancarrow DJ, Mann GJ, Holland EA, et al (1993) Confirmation of chromosome 9p linkage in familial melanoma. Am J Hum Genet 53: 936–942.

    PubMed  CAS  Google Scholar 

  7. Kamb A, Gruis NA, Weaver-Feldhaus J, et al (1994) A cell cycle regulator potentially involved in genesis of many tumor types. Science 264: 436–450.

    Article  PubMed  CAS  Google Scholar 

  8. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368: 753–756.

    Article  PubMed  CAS  Google Scholar 

  9. Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 [see comments]. Nature 366: 704–707.

    Article  PubMed  CAS  Google Scholar 

  10. Gruis NA, van der Velden PA, Sandkuijl LA, et al (1995) Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds. Nature Genetics 10: 351–353.

    Article  PubMed  CAS  Google Scholar 

  11. Hussussian C, Struewing JP, Goldstein AM, et al (1994) Germline p16 mutations in 153familial melanoma. Nature Genetics 8: 15–21.

    Article  PubMed  CAS  Google Scholar 

  12. Harland M, Meloni R, Gruis N, et al (1997) Germline mutations of the CDKN2 gene in UK melanoma families. Hum Mol Genet 6: 2061–2067.

    Article  PubMed  CAS  Google Scholar 

  13. Koh J, Enders GH, Dynlacht BD, Harlow E (1995) Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition. Nature 375: 506–510.

    Article  PubMed  CAS  Google Scholar 

  14. Soufir N, Avril MF, Chompret A, et al (1998) Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group [published erratum appears in Hum Mol Genet 1998 May;7(5):941]. Hum Mol Genet 7: 209–216.

    Article  PubMed  CAS  Google Scholar 

  15. Zuo L, Weger J, Yang Q, et al (1996) Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet 12: 97–99.

    Article  PubMed  CAS  Google Scholar 

  16. Flores JF, Pollock PM, Walker GJ, et al (1997) Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds. Oncogene 15: 2999–3005.

    Article  PubMed  CAS  Google Scholar 

  17. Platz A, Hansson J, Mansson-Brahme E, et al (1997) Screening of germline mutations in the CDKN2A and CDKN2B genes in Swedish families with hereditary cutaneous melanoma. J Natl Cancer Inst 89: 697–702.

    Article  PubMed  CAS  Google Scholar 

  18. Liu L, Goldstein AM, Tucker MA, et al (1997) Affected members of melanoma-prone families with linkage to 9p21 but lacking mutations in CDKN2A do not harbor mutations in the coding regions of either CDKN2B or p19ARF. Genes Chromosomes Cancer 19: 52–54.

    Article  PubMed  Google Scholar 

  19. Mackie RM, Andrew N, Lanyon WG, Connor JM (1998) CDKN2A germline mutations in U.K. patients with familial melanoma and multiple primary melanomas. J Invest Dermatol 111: 269–272.

    Article  PubMed  CAS  Google Scholar 

  20. Monzon J, Liu L, Brill H, et al (1998) CDKN2A mutations in multiple primary melanomas [see comments]. N Engl J Med 338: 879–887.

    Article  PubMed  CAS  Google Scholar 

  21. Whiteman DC, Milligan A, Welch J, Green AC, Hayward NK (1997) Germline CDKN2A mutations in childhood melanoma. J Natl Cancer Inst 89: 1460.

    Article  PubMed  CAS  Google Scholar 

  22. Tsao H, Zhang X, Kwitkiwski K, Finkelstein DM, Sober AJ, Haluska FG (2000) Low prevalence of germline CDKN2A and CDK4 mutations in patients with early-onset melanoma. Arch Dermatol 136: 1118–1122.

    Article  PubMed  CAS  Google Scholar 

  23. Kraemer KH, Lee MM, Andrews AD, Lambert WC (1994) The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. Arch Dermatol 130: 1018–1021.

    Article  PubMed  CAS  Google Scholar 

  24. Boni R, Vortmeyer AO, Burg G, Hofbauer G, Zhuang Z (1998) The PTEN tumour suppressor gene and malignant melanoma. Melanoma Res 8: 300–302.

    Article  PubMed  CAS  Google Scholar 

  25. Aitken J, Welch J, Duffy D, et al (1999) CDKN2A variants in a population-based sample of Queensland families with melanoma. J Natl Cancer Inst 91: 446–452.

    Article  PubMed  CAS  Google Scholar 

  26. Ung-Juurlink C (1999) American Academy of Dermatology 1999 Awards for Young Investigators in Dermatology. The prevalence of CDKN2A in patients with atypical nevi and malignant melanoma. J Am Acad Dermatol 41: 461–462.

    Google Scholar 

  27. Whiteman DC, Green A, Parson PG (1998) p53 Expression and risk factors for cutaneous melanoma:a case-control study. Int J Cancer 77: 843–848.

    Google Scholar 

  28. van-’t-Veer LJ, Burgering BM, Versteeg R, et al (1989) N-ras mutations in human cutaneous melanoma from sun-exposed body sites. Mol Cell Biol 9: 3114–3116.

    PubMed  Google Scholar 

  29. van-Elsas A, Zerp SF, van-der-Flier S, et al (1996) Relevance of ultraviolet-induced N-ras oncogene point mutations in development of primary human cutaneous melanoma [see comments]. Am J Pathol 149: 883–893.

    PubMed  CAS  Google Scholar 

  30. Chhajlani V, Wikberg JE (1992) Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. FEBS Lett 309: 417–420.

    Article  PubMed  CAS  Google Scholar 

  31. Valverde P, Healy E, Jackson I, Rees JL, Thody AJ (1995) Variants of the melanocytestimulating hormone receptor gene are associated with red hair and fair skin in humans. Nature Genetics 11: 328–330.

    Article  PubMed  CAS  Google Scholar 

  32. Smith R, Healy E, Siddiqui S, et al (1998) Melanocortin 1 receptor variants in an Irish population. J Invest Dermatol 111: 119–122.

    Article  PubMed  CAS  Google Scholar 

  33. Box NF, Wyeth JR, O’Gorman LE, Martin NG, Sturm RA (1997) Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair. Hum Mol Genet 6: 1891–1897.

    Article  PubMed  CAS  Google Scholar 

  34. Palmer JS, Duffy DL, Box NF, et al (2000) Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 66: 176–186.

    Article  PubMed  CAS  Google Scholar 

  35. Ichii-Jones F, Lear JT, Heagerty AH, et al (1998) Susceptibility to melanoma: influence of skin type and polymorphism in the melanocyte stimulating hormone receptor gene. J Invest Dermatol 111: 218–221.

    Article  PubMed  CAS  Google Scholar 

  36. Kerb R, Brockmoller J, Reum T, Roots I (1997) Deficiency of glutathione S-transferases T1 and M1 as heritable factors of increased cutaneous UV sensitivity. J Invest Dermatol 108: 229–232.

    Article  PubMed  CAS  Google Scholar 

  37. Heagerty AHM, Fitzgerald D, Smith A, et al (1994) Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous tumours. Lancet 343: 266–268.

    Article  PubMed  CAS  Google Scholar 

  38. Gorlin R (1987) Nevoid basal-cell carcinoma syndrome. Medicine 66: 98–113.

    Article  PubMed  CAS  Google Scholar 

  39. Evans D, Ladusans E, Rimmer S, Burnell L, Thakker N, Farndon P (1993) Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet 30: 460–464.

    Article  PubMed  CAS  Google Scholar 

  40. Gorlin R (1995) Nevoid basal cell carcinoma syndrome. Dermatological Clinics 13: 113–125.

    CAS  Google Scholar 

  41. Johnson R, Rothman A, Xie J, et al (1996) Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 272: 1668–1671.

    Article  PubMed  CAS  Google Scholar 

  42. Hahn H, Wicking C, Zaphiropoulos P, et al (1996) Mutations of the human homologue of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85: 841–851.

    Article  PubMed  CAS  Google Scholar 

  43. Brash DE, Ponten J (1998) Skin precancer. Cancer Surv 32: 69–113.

    PubMed  CAS  Google Scholar 

  44. Brash D, Rudolph JA, Simon JA, et al (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA 88: 10124–10128.

    Article  PubMed  CAS  Google Scholar 

  45. Rady P, Scinicariello F, Wagner RF Jr, Tyring SK (1992) p53 mutations in basal cell carcinomas. Cancer Res 52: 3804–3806.

    Google Scholar 

  46. Campbell C, Quinn A, Ro Y, Angus B, Rees J (1993) p53 mutations are common and early evens that precede tumor invasion in squamous cell neoplasia of the skin. J Invest Dermatol 100: 746–748.

    Google Scholar 

  47. Bastiaens MT, Struyk L, Tjong-A-Hung SP, et al (2001) Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening. Mol Carcinogen 30: 56–61.

    Article  CAS  Google Scholar 

  48. Wei Q, Matanoski G, Farmer E, Hedayati M, Grossman L (1993) DNA repair and aging in basal cell carcinoma: a molecular epidemiologic study. Proc Natl Acad Sci USA 90: 1614–1618.

    Article  PubMed  CAS  Google Scholar 

  49. Dybdahl M, Frentz G, Vogel U, Wallin H, Nexo B (1999) Low DNA repair is a risk factor in skin carcinogenesis: a study of basal cell carcinoma in psoriasis patients. Mutation Res 433: 15–22.

    Article  PubMed  CAS  Google Scholar 

  50. Hall J, English D, Artuso M, Armstrong B, Winter M (1994) DNA repair capacity as a risk factor for non-melanocytic skin cancer–a molecular epidemiologic study. Int J Cancer 58: 179–184.

    Article  PubMed  CAS  Google Scholar 

  51. Benhamou S, Sarasin A (2000) Variability in nucleotide excision repair and cancer risk: a review. Mutation Res 462: 149–158.

    Article  PubMed  CAS  Google Scholar 

  52. Unden A, Holmberg E, Lundh-Rozell B, et al (1996) Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin Syndrome:Different in vivo mechanisms of PTCH inactivation. Cancer Res 56: 4562–4565.

    PubMed  CAS  Google Scholar 

  53. Gailani M, Stahle-Backdahl M, Leffell D, et al (1996) The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet 14: 78–81.

    Article  PubMed  CAS  Google Scholar 

  54. Evans T, Boonchai W, Shanley S, et al (2000) The spectrum of patched mutations in a collection of Australian basal cell carcinomas. Human Mutat 16: 43–48.

    Article  CAS  Google Scholar 

  55. Jones F, Ramachandran S, Lear J, et al (1999) The melanocyte stimulating hormone receptor polymorphism: association of the V92M and A294H alleles with basal cell carcinoma. Clinica Chimica Acta 282: 125–134.

    Article  CAS  Google Scholar 

  56. Lear T, Smith A, Strange R, Fryer A (2000) Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy. Br J Dermatol 142: 8–15.

    Article  PubMed  CAS  Google Scholar 

  57. Kefford RF, Newton-Bishop JA, Bergman W, Tucker MA (1999) Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol 17: 3245–3251.

    PubMed  CAS  Google Scholar 

  58. van-Ommen GJ, Bakker E, den-Dunnen JT (1999) The human genome project and the future of diagnostics, treatment, and prevention. Lancet 354 Suppl 1: SI5–S10.

    Google Scholar 

  59. Collins FS (1999) Shattuck Lecture–Medical and societal consequences of the Human Genome Project. N Engl J Med 341: 28–37.

    Article  PubMed  CAS  Google Scholar 

  60. Vinei P, Schulte P, McMichael AJ (2001) Misconceptions about the use of genetic tests in populations. Lancet 357: 709–712.

    Article  Google Scholar 

  61. Piepkorn M (2000) Melanoma genetics: an update with focus on the CDKN2A(p16)/ARF tumor suppressors. J Am Acad Dermatol 42: 705–722.

    Article  PubMed  CAS  Google Scholar 

  62. Harland M, Holland EA, Ghiorzo P, et al (2000) Mutation screening of the CDKN2A promoter in melanoma families. Genes Chromosomes Cancer 28: 45–57.

    Article  PubMed  CAS  Google Scholar 

  63. Battistutta D, Palmer J, Walters M, Walker G, Nancarrow D, Hayward N (1994) Incidence of familial melanoma and MLM2 gene. Lancet 344: 1607–1608.

    Article  PubMed  CAS  Google Scholar 

  64. MacLennan R, Green AC, McLeod GRC, Martin NG (1992) Increasing incidence of cutaneous melanoma in Queensland, Australia. J Natl Cancer Inst 84: 1427–1432.

    Article  PubMed  CAS  Google Scholar 

  65. Yarosh DB, O’Connor A, Alas L, Potten C, Wolf P (1999) Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies. Photochem Photobiol 69: 136–140.

    PubMed  CAS  Google Scholar 

  66. Yarosh D, Klein J, O’Connor A, et al (2001) Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Lancet 357: 926–929.

    Article  PubMed  CAS  Google Scholar 

  67. Jackson R (2000) Updated New Zealand cardiovascular disease risk-benefit prediction guide. Br Med J 320: 709–710.

    Article  CAS  Google Scholar 

  68. Isles CG, Ritchie LD, Murchie P, Norrie J (2000) Risk assessment in primary prevention of coronary heart disease: randomised comparison of three scoring methods. Br Med J 320: 690–691.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Population and Clinical Sciences Division, Queensland Institute of Medical Research, Herston, Queensland, Australia

    David Whiteman B.Med.Sc., M.B., B.S. (Hons), Ph.D.

Authors
  1. David Whiteman B.Med.Sc., M.B., B.S. (Hons), Ph.D.
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  2. Rachel Neale Ph.D.
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Editor information

Editors and Affiliations

  1. Centre for Behavioural Research in Cancer, The Cancer Council Victoria, Melbourne, Victoria, Australia

    David Hill Ph.D.

  2. National Cancer Control Initiative, Melbourne, Victoria, Australia

    J. Mark Elwood M.D., D.Sc.

  3. Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia

    Dallas R. English Ph.D.

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© 2004 Springer Science+Business Media Dordrecht

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Whiteman, D., Neale, R. (2004). The role of genetics in the prevention of skin cancer. In: Hill, D., Elwood, J.M., English, D.R. (eds) Prevention of Skin Cancer. Cancer Prevention — Cancer Causes, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0511-0_7

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  • DOI: https://doi.org/10.1007/978-94-017-0511-0_7

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-6346-5

  • Online ISBN: 978-94-017-0511-0

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