title: Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom.
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%).
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Harland
authors.affiliation: Cancer Epidemiology and Services Research (CESR), Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cust
authors.affiliation: 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.
authors.forename: Celia
authors.initials: C
authors.lastname: Badenas
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Chang
authors.affiliation: Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Holland
authors.affiliation: 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.
authors.forename: Paula
authors.initials: P
authors.lastname: Aguilera
authors.affiliation: Viertel Centre for Research in Cancer Control, The Cancer Council Queensland, Spring Hill, Brisbane, Australia.
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Aitken
authors.affiliation: Cancer Epidemiology and Services Research (CESR), Sydney School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
authors.affiliation: 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.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrera
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: May
authors.initials: M
authors.lastname: Chan
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Gascoyne
authors.affiliation: Centre for Epidemiology & Biostatistics, School of Population Health, University of Melbourne, Melbourne, Australia ; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Agha-Hamilton
authors.affiliation: Centre for Epidemiology & Biostatistics, School of Population Health, University of Melbourne, Melbourne, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Centre for Epidemiology & Biostatistics, School of Population Health, University of Melbourne, Melbourne, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.affiliation: Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.affiliation: Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
authors.forename: Isabel
authors.initials: I
authors.lastname: Kolm
authors.affiliation: Genomics Facility, Leeds Cancer Research UK Centre, University of Leeds, Leeds, UK.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lowery
authors.affiliation: 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.
authors.forename: Josep
authors.initials: J
authors.lastname: Malvehy
authors.affiliation: Dermatology Department and Biochemistry and Molecular Genetics Department, Melanoma Unit, Hospital Clinic, Instituto de Investigaciones Biomédicas August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Zighereda
authors.initials: Z
authors.lastname: Ogbah
authors.affiliation: 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.
authors.forename: Joan-Anton
authors.initials: JA
authors.lastname: Puig-Butille
authors.affiliation: Medicina Laboral, Lafarge Cementos y Finanzauto, S.A., Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Orihuela-Segalés
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Juliette A
authors.initials: JA
authors.lastname: Randerson-Moor
authors.affiliation: Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Schmid
authors.affiliation: Genomics Facility, Leeds Cancer Research UK Centre, University of Leeds, Leeds, UK.
authors.forename: Claire F
authors.initials: CF
authors.lastname: Taylor
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Whitaker
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.affiliation: Westmead Institute for Cancer Research and Melanoma Institute, Australia, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Newton-Bishop
authors.affiliation: 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.
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
keywords: CDKN2A; Family history; Melanoma; Multiple primaries; Population-based