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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.

Author information

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.

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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