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. 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

Mark Harland  1 , Anne E Cust  2 , Celia Badenas  3 , Yu-Mei Chang  1 , Elizabeth A Holland  4 , Paula Aguilera  3 , Joanne F Aitken  5 , Bruce K Armstrong  2 , Jennifer H Barrett  1 , Cristina Carrera  3 , May Chan  1 , Joanne Gascoyne  1 , Graham G Giles  6 , Chantelle Agha-Hamilton  4 , John L Hopper  7 , Mark A Jenkins  7 , Peter A Kanetsky  8 , Richard F Kefford  4 , Isabel Kolm  4 , Johanna Lowery  9 , Josep Malvehy  3 , Zighereda Ogbah  10 , Joan-Anton Puig-Butille  3 , Jordi Orihuela-Segalés  11 , Juliette A Randerson-Moor  1 , Helen Schmid  4 , Claire F Taylor  9 , Linda Whitaker  1 , D Timothy Bishop  1 , Graham J Mann  4 , Julia A Newton-Bishop  1 , Susana Puig  3
Affiliations

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

Mark Harland et al. Hered Cancer Clin Pract. .

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.

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