Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies

2.50
Hdl Handle:
http://hdl.handle.net/2336/67295
Title:
Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies
Authors:
Karppinen, S-M; Barkardottir, R B; Backenhorn, K; Sydenham, T; Syrjäkoski, K; Schleutker, J; Ikonen, T; Pylkäs, K; Rapakko, K; Erkko, H; Johannesdottir, G; Gerdes, A-M; Thomassen, M; Agnarsson, B A; Grip, M; Kallioniemi, A; Kere, J; Aaltonen, L A; Arason, A; Møller, P; Kruse, T A; Borg, A; Winqvist, R
Citation:
J. Med. Genet. 2006, 43(11):856-62
Issue Date:
1-Nov-2006
Abstract:
BACKGROUND: BARD1 was originally identified as a BRCA1-interacting protein but has also been described in tumour-suppressive functions independent of BRCA1. Several studies have indicated that the BARD1 gene is a potential target for germline changes predisposing to breast and ovarian cancer. The C-terminal Cys557Ser change has previously been uncovered to associate with an increased risk of breast cancer and was recently shown to result in defective apoptotic activities. AIM AND METHODS: Conformation-sensitive gel electrophoresis, minisequencing, TaqMan assays, denaturing high-performance liquid chromatography analysis and DNA sequencing were used to investigate the prevalence of the Cys557Ser allele in a large Nordic case-control study cohort consisting of 2906 patients with breast or ovarian cancer, 734 with prostate cancer, 188 with colorectal cancer, 128 men with breast cancer, and 3591 controls from Finland, Iceland, Denmark, Sweden and Norway. RESULTS: The frequency of the BARD1 Cys557Ser variant seemed to increase among patients from families with breast or ovarian cancer lacking BRCA1 or BRCA2 mutations: a significant difference was obtained compared with controls (6.8% v 2.7%; p<0.001; odds ratio (OR) 2.6; 95% confidence interval (CI) 1.7 to 4.0) and with patients from BRCA1/BRCA2 mutation-positive families (6.8% v 2.2%; p = 0.01; OR 3.2; 95% CI 1.2 to 8.3). In contrast, no major association with male breast, ovarian, colorectal or prostate cancer was observed. Additionally, a novel BARD1 allele resulting in Ser558Pro was identified in familial breast cancer cases. CONCLUSION: These results provide further evidence that BARD1 Cys557Ser confers a slightly increased risk of breast cancer in women.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://jmg.bmj.com/cgi/content/abstract/43/11/856

Full metadata record

DC FieldValue Language
dc.contributor.authorKarppinen, S-M-
dc.contributor.authorBarkardottir, R B-
dc.contributor.authorBackenhorn, K-
dc.contributor.authorSydenham, T-
dc.contributor.authorSyrjäkoski, K-
dc.contributor.authorSchleutker, J-
dc.contributor.authorIkonen, T-
dc.contributor.authorPylkäs, K-
dc.contributor.authorRapakko, K-
dc.contributor.authorErkko, H-
dc.contributor.authorJohannesdottir, G-
dc.contributor.authorGerdes, A-M-
dc.contributor.authorThomassen, M-
dc.contributor.authorAgnarsson, B A-
dc.contributor.authorGrip, M-
dc.contributor.authorKallioniemi, A-
dc.contributor.authorKere, J-
dc.contributor.authorAaltonen, L A-
dc.contributor.authorArason, A-
dc.contributor.authorMøller, P-
dc.contributor.authorKruse, T A-
dc.contributor.authorBorg, A-
dc.contributor.authorWinqvist, R-
dc.date.accessioned2009-05-05T13:41:24Z-
dc.date.available2009-05-05T13:41:24Z-
dc.date.issued2006-11-01-
dc.date.submitted2009-05-05-
dc.identifier.citationJ. Med. Genet. 2006, 43(11):856-62en
dc.identifier.issn1468-6244-
dc.identifier.pmid16825437-
dc.identifier.doi10.1136/jmg.2006.041731-
dc.identifier.urihttp://hdl.handle.net/2336/67295-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: BARD1 was originally identified as a BRCA1-interacting protein but has also been described in tumour-suppressive functions independent of BRCA1. Several studies have indicated that the BARD1 gene is a potential target for germline changes predisposing to breast and ovarian cancer. The C-terminal Cys557Ser change has previously been uncovered to associate with an increased risk of breast cancer and was recently shown to result in defective apoptotic activities. AIM AND METHODS: Conformation-sensitive gel electrophoresis, minisequencing, TaqMan assays, denaturing high-performance liquid chromatography analysis and DNA sequencing were used to investigate the prevalence of the Cys557Ser allele in a large Nordic case-control study cohort consisting of 2906 patients with breast or ovarian cancer, 734 with prostate cancer, 188 with colorectal cancer, 128 men with breast cancer, and 3591 controls from Finland, Iceland, Denmark, Sweden and Norway. RESULTS: The frequency of the BARD1 Cys557Ser variant seemed to increase among patients from families with breast or ovarian cancer lacking BRCA1 or BRCA2 mutations: a significant difference was obtained compared with controls (6.8% v 2.7%; p<0.001; odds ratio (OR) 2.6; 95% confidence interval (CI) 1.7 to 4.0) and with patients from BRCA1/BRCA2 mutation-positive families (6.8% v 2.2%; p = 0.01; OR 3.2; 95% CI 1.2 to 8.3). In contrast, no major association with male breast, ovarian, colorectal or prostate cancer was observed. Additionally, a novel BARD1 allele resulting in Ser558Pro was identified in familial breast cancer cases. CONCLUSION: These results provide further evidence that BARD1 Cys557Ser confers a slightly increased risk of breast cancer in women.en
dc.language.isoenen
dc.publisherBritish Medical Associationen
dc.relation.urlhttp://jmg.bmj.com/cgi/content/abstract/43/11/856en
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshAllelesen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshBreast Neoplasms, Maleen
dc.subject.meshCase-Control Studiesen
dc.subject.meshCohort Studiesen
dc.subject.meshColorectal Neoplasmsen
dc.subject.meshDNA Mutational Analysisen
dc.subject.meshFemaleen
dc.subject.meshGenes, BRCA1en
dc.subject.meshGenes, BRCA2en
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenetic Screeningen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMutation, Missenseen
dc.subject.meshOvarian Neoplasmsen
dc.subject.meshProstatic Neoplasmsen
dc.subject.meshTumor Suppressor Proteinsen
dc.subject.meshUbiquitin-Protein Ligasesen
dc.titleNordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignanciesen
dc.typeArticleen
dc.contributor.departmentDepartment of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland.en
dc.identifier.journalJournal of medical geneticsen

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