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
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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 t...
Published in: | Journal of Medical Genetics |
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British Medical Association
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Online Access: | http://hdl.handle.net/2336/67295 https://doi.org/10.1136/jmg.2006.041731 |
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ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/67295 2023-05-15T16:52:47+02:00 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 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 Department of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland. 2009-05-05 http://hdl.handle.net/2336/67295 https://doi.org/10.1136/jmg.2006.041731 en eng British Medical Association http://jmg.bmj.com/cgi/content/abstract/43/11/856 J. Med. Genet. 2006, 43(11):856-62 1468-6244 16825437 doi:10.1136/jmg.2006.041731 http://hdl.handle.net/2336/67295 Journal of medical genetics Adolescent Adult Aged 80 and over Alleles Breast Neoplasms Male Case-Control Studies Cohort Studies Colorectal Neoplasms DNA Mutational Analysis Female Genes BRCA1 BRCA2 Genetic Predisposition to Disease Genetic Screening Humans Middle Aged Mutation Missense Ovarian Neoplasms Prostatic Neoplasms Tumor Suppressor Proteins Ubiquitin-Protein Ligases Article 2009 ftlandspitaliuni https://doi.org/10.1136/jmg.2006.041731 2022-05-29T08:21:20Z To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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. Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive Norway Journal of Medical Genetics 43 11 856 862 |
institution |
Open Polar |
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Hirsla - Landspítali University Hospital research archive |
op_collection_id |
ftlandspitaliuni |
language |
English |
topic |
Adolescent Adult Aged 80 and over Alleles Breast Neoplasms Male Case-Control Studies Cohort Studies Colorectal Neoplasms DNA Mutational Analysis Female Genes BRCA1 BRCA2 Genetic Predisposition to Disease Genetic Screening Humans Middle Aged Mutation Missense Ovarian Neoplasms Prostatic Neoplasms Tumor Suppressor Proteins Ubiquitin-Protein Ligases |
spellingShingle |
Adolescent Adult Aged 80 and over Alleles Breast Neoplasms Male Case-Control Studies Cohort Studies Colorectal Neoplasms DNA Mutational Analysis Female Genes BRCA1 BRCA2 Genetic Predisposition to Disease Genetic Screening Humans Middle Aged Mutation Missense Ovarian Neoplasms Prostatic Neoplasms Tumor Suppressor Proteins Ubiquitin-Protein Ligases 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 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 |
topic_facet |
Adolescent Adult Aged 80 and over Alleles Breast Neoplasms Male Case-Control Studies Cohort Studies Colorectal Neoplasms DNA Mutational Analysis Female Genes BRCA1 BRCA2 Genetic Predisposition to Disease Genetic Screening Humans Middle Aged Mutation Missense Ovarian Neoplasms Prostatic Neoplasms Tumor Suppressor Proteins Ubiquitin-Protein Ligases |
description |
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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. |
author2 |
Department of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland. |
format |
Article in Journal/Newspaper |
author |
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 |
author_facet |
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 |
author_sort |
Karppinen, S-M |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
British Medical Association |
publishDate |
2009 |
url |
http://hdl.handle.net/2336/67295 https://doi.org/10.1136/jmg.2006.041731 |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://jmg.bmj.com/cgi/content/abstract/43/11/856 J. Med. Genet. 2006, 43(11):856-62 1468-6244 16825437 doi:10.1136/jmg.2006.041731 http://hdl.handle.net/2336/67295 Journal of medical genetics |
op_doi |
https://doi.org/10.1136/jmg.2006.041731 |
container_title |
Journal of Medical Genetics |
container_volume |
43 |
container_issue |
11 |
container_start_page |
856 |
op_container_end_page |
862 |
_version_ |
1766043173541380096 |