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

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 ca...

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Autores principales: Harland, Mark, Cust, Anne E, Badenas, Celia, Chang, Yu-Mei, Holland, Elizabeth A, Aguilera, Paula, Aitken, Joanne F, Armstrong, Bruce K, Barrett, Jennifer H, Carrera, Cristina, Chan, May, Gascoyne, Joanne, Giles, Graham G, Agha-Hamilton, Chantelle, Hopper, John L, Jenkins, Mark A, Kanetsky, Peter A, Kefford, Richard F, Kolm, Isabel, Lowery, Johanna, Malvehy, Josep, Ogbah, Zighereda, Puig-Butille, Joan-Anton, Orihuela-Segalés, Jordi, Randerson-Moor, Juliette A, Schmid, Helen, Taylor, Claire F, Whitaker, Linda, Bishop, D Timothy, Mann, Graham J, Newton-Bishop, Julia A, Puig, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361137/
https://www.ncbi.nlm.nih.gov/pubmed/25780468
http://dx.doi.org/10.1186/1897-4287-12-20
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author Harland, Mark
Cust, Anne E
Badenas, Celia
Chang, Yu-Mei
Holland, Elizabeth A
Aguilera, Paula
Aitken, Joanne F
Armstrong, Bruce K
Barrett, Jennifer H
Carrera, Cristina
Chan, May
Gascoyne, Joanne
Giles, Graham G
Agha-Hamilton, Chantelle
Hopper, John L
Jenkins, Mark A
Kanetsky, Peter A
Kefford, Richard F
Kolm, Isabel
Lowery, Johanna
Malvehy, Josep
Ogbah, Zighereda
Puig-Butille, Joan-Anton
Orihuela-Segalés, Jordi
Randerson-Moor, Juliette A
Schmid, Helen
Taylor, Claire F
Whitaker, Linda
Bishop, D Timothy
Mann, Graham J
Newton-Bishop, Julia A
Puig, Susana
author_facet Harland, Mark
Cust, Anne E
Badenas, Celia
Chang, Yu-Mei
Holland, Elizabeth A
Aguilera, Paula
Aitken, Joanne F
Armstrong, Bruce K
Barrett, Jennifer H
Carrera, Cristina
Chan, May
Gascoyne, Joanne
Giles, Graham G
Agha-Hamilton, Chantelle
Hopper, John L
Jenkins, Mark A
Kanetsky, Peter A
Kefford, Richard F
Kolm, Isabel
Lowery, Johanna
Malvehy, Josep
Ogbah, Zighereda
Puig-Butille, Joan-Anton
Orihuela-Segalés, Jordi
Randerson-Moor, Juliette A
Schmid, Helen
Taylor, Claire F
Whitaker, Linda
Bishop, D Timothy
Mann, Graham J
Newton-Bishop, Julia A
Puig, Susana
author_sort Harland, Mark
collection PubMed
description 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%). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1897-4287-12-20) contains supplementary material, which is available to authorized users.
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spelling pubmed-43611372015-03-17 Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom Harland, Mark Cust, Anne E Badenas, Celia Chang, Yu-Mei Holland, Elizabeth A Aguilera, Paula Aitken, Joanne F Armstrong, Bruce K Barrett, Jennifer H Carrera, Cristina Chan, May Gascoyne, Joanne Giles, Graham G Agha-Hamilton, Chantelle Hopper, John L Jenkins, Mark A Kanetsky, Peter A Kefford, Richard F Kolm, Isabel Lowery, Johanna Malvehy, Josep Ogbah, Zighereda Puig-Butille, Joan-Anton Orihuela-Segalés, Jordi Randerson-Moor, Juliette A Schmid, Helen Taylor, Claire F Whitaker, Linda Bishop, D Timothy Mann, Graham J Newton-Bishop, Julia A Puig, Susana Hered Cancer Clin Pract Research 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%). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1897-4287-12-20) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-20 /pmc/articles/PMC4361137/ /pubmed/25780468 http://dx.doi.org/10.1186/1897-4287-12-20 Text en © Harland et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Harland, Mark
Cust, Anne E
Badenas, Celia
Chang, Yu-Mei
Holland, Elizabeth A
Aguilera, Paula
Aitken, Joanne F
Armstrong, Bruce K
Barrett, Jennifer H
Carrera, Cristina
Chan, May
Gascoyne, Joanne
Giles, Graham G
Agha-Hamilton, Chantelle
Hopper, John L
Jenkins, Mark A
Kanetsky, Peter A
Kefford, Richard F
Kolm, Isabel
Lowery, Johanna
Malvehy, Josep
Ogbah, Zighereda
Puig-Butille, Joan-Anton
Orihuela-Segalés, Jordi
Randerson-Moor, Juliette A
Schmid, Helen
Taylor, Claire F
Whitaker, Linda
Bishop, D Timothy
Mann, Graham J
Newton-Bishop, Julia A
Puig, Susana
Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom
title Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom
title_full Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom
title_fullStr Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom
title_full_unstemmed Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom
title_short Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom
title_sort prevalence and predictors of germline cdkn2a mutations for melanoma cases from australia, spain and the united kingdom
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361137/
https://www.ncbi.nlm.nih.gov/pubmed/25780468
http://dx.doi.org/10.1186/1897-4287-12-20
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