2.50
Hdl Handle:
http://hdl.handle.net/2336/42363
Title:
CDKN2A mutations and melanoma risk in the Icelandic population.
Authors:
Goldstein, A M; Stacey, S N; Olafsson, J H; Jonsson, G F; Helgason, A; Sulem, P; Sigurgeirsson, B; Benediktsdottir, K R; Thorisdottir, K; Ragnarsson, R; Kjartansson, J; Kostic, J; Masson, G; Kristjansson, K; Gulcher, J R; Kong, A; Thorsteinsdottir, U; Rafnar, T; Tucker, M A; Stefansson, K
Citation:
J. Med. Genet. 2008, 45(5):284-9
Issue Date:
1-May-2008
Abstract:
BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1136/jmg.2007.055376

Full metadata record

DC FieldValue Language
dc.contributor.authorGoldstein, A M-
dc.contributor.authorStacey, S N-
dc.contributor.authorOlafsson, J H-
dc.contributor.authorJonsson, G F-
dc.contributor.authorHelgason, A-
dc.contributor.authorSulem, P-
dc.contributor.authorSigurgeirsson, B-
dc.contributor.authorBenediktsdottir, K R-
dc.contributor.authorThorisdottir, K-
dc.contributor.authorRagnarsson, R-
dc.contributor.authorKjartansson, J-
dc.contributor.authorKostic, J-
dc.contributor.authorMasson, G-
dc.contributor.authorKristjansson, K-
dc.contributor.authorGulcher, J R-
dc.contributor.authorKong, A-
dc.contributor.authorThorsteinsdottir, U-
dc.contributor.authorRafnar, T-
dc.contributor.authorTucker, M A-
dc.contributor.authorStefansson, K-
dc.date.accessioned2008-12-15T13:34:59Z-
dc.date.available2008-12-15T13:34:59Z-
dc.date.issued2008-05-01-
dc.date.submitted2008-12-15-
dc.identifier.citationJ. Med. Genet. 2008, 45(5):284-9en
dc.identifier.issn0022-2593-
dc.identifier.pmid18178632-
dc.identifier.doi10.1136/jmg.2007.055376-
dc.identifier.urihttp://hdl.handle.net/2336/42363-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.en
dc.language.isoenen
dc.publisherBritish Medical Associationen
dc.relation.urlhttp://dx.doi.org/10.1136/jmg.2007.055376en
dc.subject.meshAllelesen
dc.subject.meshAustraliaen
dc.subject.meshCase-Control Studiesen
dc.subject.meshGene Frequencyen
dc.subject.meshGenes, p16en
dc.subject.meshGenotypeen
dc.subject.meshGerm-Line Mutationen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshMelanomaen
dc.subject.meshNorth Americaen
dc.subject.meshPopulation Groupsen
dc.subject.meshRisk Factorsen
dc.titleCDKN2A mutations and melanoma risk in the Icelandic population.en
dc.typeArticleen
dc.identifier.eissn1468-6244-
dc.contributor.departmentGenetic Epidemiology Branch, Division of Cancer Epidemiologyand Genetics/NCI/NIH/DHHS, Executive Plaza South, Room 7004, 6120 Executive Blvd MSC 7236, Bethesda, MD 20892-7236, USA. goldstea@exchange.nih.goven
dc.identifier.journalJournal of medical geneticsen

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