Display options
Cite
Harland M, Cust AE, Badenas C, et al. Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom. Hered Cancer Clin Pract. 2014;12(1):20doi: 10.1186/1897-4287-12-20.
Harland, M., Cust, A. E., Badenas, C., Chang, Y. M., Holland, E. A., Aguilera, P., Aitken, J. F., Armstrong, B. K., Barrett, J. H., Carrera, C., Chan, M., Gascoyne, J., Giles, G. G., Agha-Hamilton, C., Hopper, J. L., Jenkins, M. A., Kanetsky, P. A., Kefford, R. F., Kolm, I., Lowery, J., Malvehy, J., Ogbah, Z., Puig-Butille, J. A., Orihuela-Segalés, J., Randerson-Moor, J. A., Schmid, H., Taylor, C. F., Whitaker, L., Bishop, D. T., Mann, G. J., Newton-Bishop, J. A., & Puig, S. (2014). Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom. Hereditary cancer in clinical practice, 12(1), 20. https://doi.org/10.1186/1897-4287-12-20
Harland, Mark, et al. "Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom." Hereditary cancer in clinical practice vol. 12,1 (2014): 20. doi: https://doi.org/10.1186/1897-4287-12-20
Harland M, Cust AE, Badenas C, Chang YM, Holland EA, Aguilera P, Aitken JF, Armstrong BK, Barrett JH, Carrera C, Chan M, Gascoyne J, Giles GG, Agha-Hamilton C, Hopper JL, Jenkins MA, Kanetsky PA, Kefford RF, Kolm I, Lowery J, Malvehy J, Ogbah Z, Puig-Butille JA, Orihuela-Segalés J, Randerson-Moor JA, Schmid H, Taylor CF, Whitaker L, Bishop DT, Mann GJ, Newton-Bishop JA, Puig S. Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom. Hered Cancer Clin Pract. 2014 Nov 20;12(1):20. doi: 10.1186/1897-4287-12-20. eCollection 2014. PMID: 25780468; PMCID: PMC4361137.
Copy Download .nbib Format: NLM
Share it on

Hered Cancer Clin Pract. 2014 Nov 20;12(1):20. doi: 10.1186/1897-4287-12-20. eCollection 2014.

Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom.

Hereditary cancer in clinical practice

Mark Harland, Anne E Cust, Celia Badenas, Yu-Mei Chang, Elizabeth A Holland, Paula Aguilera, Joanne F Aitken, Bruce K Armstrong, Jennifer H Barrett, Cristina Carrera, May Chan, Joanne Gascoyne, Graham G Giles, Chantelle Agha-Hamilton, John L Hopper, Mark A Jenkins, Peter A Kanetsky, Richard F Kefford, Isabel Kolm, Johanna Lowery, Josep Malvehy, Zighereda Ogbah, Joan-Anton Puig-Butille, Jordi Orihuela-Segalés, Juliette A Randerson-Moor, Helen Schmid, Claire F Taylor, Linda Whitaker, D Timothy Bishop, Graham J Mann, Julia A Newton-Bishop, Susana Puig

Affiliations

  1. Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
  2. Cancer Epidemiology and Services Research (CESR), Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
  3. Dermatology Department and Biochemistry and Molecular Genetics Department, Melanoma Unit, Hospital Clinic, Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain ; Centro Investigación Biomédica en Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
  4. Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
  5. Viertel Centre for Research in Cancer Control, The Cancer Council Queensland, Spring Hill, Brisbane, Australia.
  6. Centre for Epidemiology & Biostatistics, School of Population Health, University of Melbourne, Melbourne, Australia ; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
  7. Centre for Epidemiology & Biostatistics, School of Population Health, University of Melbourne, Melbourne, Australia.
  8. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL USA.
  9. Genomics Facility, Leeds Cancer Research UK Centre, University of Leeds, Leeds, UK.
  10. Dermatology Department and Biochemistry and Molecular Genetics Department, Melanoma Unit, Hospital Clinic, Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
  11. Medicina Laboral, Lafarge Cementos y Finanzauto, S.A., Barcelona, Spain.

PMID: 25780468 PMCID: PMC4361137 DOI: 10.1186/1897-4287-12-20

Abstract

BACKGROUND: Mutations in the CDKN2A and CDK4 genes predispose to melanoma. From three case-control studies of cutaneous melanoma, we estimated the prevalence and predictors of these mutations for people from regions with widely differing latitudes and melanoma incidence.

METHODS: Population-based cases and controls from the United Kingdom (1586 cases, 499 controls) and Australia (596 early-onset cases, 476 controls), and a hospital-based series from Spain (747 cases, 109 controls), were screened for variants in all exons of CDKN2A and the p16INK4A binding domain of CDK4.

RESULTS: The prevalence of mutations for people with melanoma was similar across regions: 2.3%, 2.5% and 2.0% for Australia, Spain and the United Kingdom respectively. The strongest predictors of carrying a mutation were having multiple primaries (odds ratio (OR) = 5.4, 95% confidence interval (CI: 2.5, 11.6) for 2 primaries and OR = 32.4 (95% CI: 14.7, 71.2) for 3 or more compared with 1 primary only); and family history (OR = 3.8; 95% CI:1.89, 7.5) for 1 affected first- or second-degree relative and OR = 23.2 (95% CI: 11.3, 47.6) for 2 or more compared with no affected relatives). Only 1.1% of melanoma cases with neither a family history nor multiple primaries had mutations.

CONCLUSIONS: There is a low probability (<2%) of detecting a germline CDKN2A mutation in people with melanoma except for those with a strong family history of melanoma (≥2 affected relatives, 25%), three or more primary melanomas (29%), or more than one primary melanoma who also have other affected relatives (27%).

Keywords: CDKN2A; Family history; Melanoma; Multiple primaries; Population-based

References

  1. J Med Genet. 2011 Apr;48(4):266-72 - PubMed
  2. J Invest Dermatol. 2002 Dec;119(6):1355-60 - PubMed
  3. J Natl Cancer Inst. 1997 Oct 1;89(19):1460 - PubMed
  4. Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1520-5 - PubMed
  5. Eur J Cancer. 2008 Jun;44(9):1269-74 - PubMed
  6. J Med Genet. 2008 May;45(5):284-9 - PubMed
  7. Lancet. 2009 Aug 1;374(9687):362-5 - PubMed
  8. Hum Mutat. 2011 Aug;32(8):900-11 - PubMed
  9. Br J Dermatol. 2011 Dec;165(6):1219-22 - PubMed
  10. Br J Dermatol. 2009 Sep;161(3):536-41 - PubMed
  11. J Clin Oncol. 2005 May 1;23(13):3043-51 - PubMed
  12. Int J Cancer. 2001 Nov 20;95(6):388-93 - PubMed
  13. Nat Genet. 1996 Jan;12(1):97-9 - PubMed
  14. Hum Mol Genet. 1998 Feb;7(2):209-16 - PubMed
  15. Am J Epidemiol. 2009 Dec 15;170(12):1541-54 - PubMed
  16. J Invest Dermatol. 2002 Oct;119(4):961-5 - PubMed
  17. Cancer Res. 2005 Feb 1;65(3):835-9 - PubMed
  18. J Invest Dermatol. 2007 May;127(5):1234-43 - PubMed
  19. J Invest Dermatol. 2006 Jul;126(7):1657-60 - PubMed
  20. Cancer Epidemiol. 2011 Dec;35(6):e116-20 - PubMed
  21. Melanoma Res. 2007 Jun;17(3):185-91 - PubMed
  22. Nat Genet. 1994 Sep;8(1):23-6 - PubMed
  23. J Am Acad Dermatol. 2009 Oct;61(4):677.e1-14 - PubMed
  24. Ann Surg Oncol. 2012 Jun;19(6):1782-9 - PubMed
  25. Genes Chromosomes Cancer. 2008 Feb;47(2):175-84 - PubMed
  26. J Med Genet. 2007 Feb;44(2):99-106 - PubMed
  27. J Invest Dermatol. 2006 Mar;126(3):660-6 - PubMed
  28. J Am Acad Dermatol. 2012 Dec;67(6):1257-64 - PubMed
  29. Hum Mol Genet. 2001 Nov 1;10(23):2679-86 - PubMed
  30. Biochem Soc Trans. 2009 Apr;37(Pt 2):433-7 - PubMed
  31. N Engl J Med. 1998 Mar 26;338(13):879-87 - PubMed
  32. Eur J Cancer. 2009 Dec;45(18):3271-81 - PubMed
  33. Acta Biochim Pol. 2007;54(1):119-24 - PubMed

Publication Types

Grant support