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

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 LoweryJosep 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

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24 Citations (Scopus)


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%).

Original languageEnglish
Article number20
Number of pages10
JournalHereditary Cancer in Clinical Practice
Issue number1
Publication statusPublished - 20 Nov 2014
Externally publishedYes


  • CDKN2A
  • Family history
  • Melanoma
  • Multiple primaries
  • Population-based

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