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
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...
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Language: | English |
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Online Access: | https://lup.lub.lu.se/record/378323 https://doi.org/10.1136/jmg.2006.041731 |
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ftulundlup:oai:lup.lub.lu.se:14637813-bd56-47a5-8610-60ad65b0803e 2023-05-15T16:51:42+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. Harbst, Katja Sydenham, T. Syrjakoski, K. Schleutker, J. Ikonen, T. Pylkas, 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. Moller, P. Kruse, T. A. Borg, Åke Winqvist, R. 2006 https://lup.lub.lu.se/record/378323 https://doi.org/10.1136/jmg.2006.041731 eng eng BMJ Publishing Group https://lup.lub.lu.se/record/378323 http://dx.doi.org/10.1136/jmg.2006.041731 wos:000241778500004 scopus:33751242758 Journal of Medical Genetics; 43(11), pp 856-862 (2006) ISSN: 0022-2593 Medical Genetics contributiontojournal/article info:eu-repo/semantics/article text 2006 ftulundlup https://doi.org/10.1136/jmg.2006.041731 2023-02-01T23:28:07Z 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 Lund University Publications (LUP) Norway Journal of Medical Genetics 43 11 856 862 |
institution |
Open Polar |
collection |
Lund University Publications (LUP) |
op_collection_id |
ftulundlup |
language |
English |
topic |
Medical Genetics |
spellingShingle |
Medical Genetics Karppinen, S. -M. Barkardottir, R. B. Harbst, Katja Sydenham, T. Syrjakoski, K. Schleutker, J. Ikonen, T. Pylkas, 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. Moller, P. Kruse, T. A. Borg, Åke 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 |
Medical Genetics |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Karppinen, S. -M. Barkardottir, R. B. Harbst, Katja Sydenham, T. Syrjakoski, K. Schleutker, J. Ikonen, T. Pylkas, 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. Moller, P. Kruse, T. A. Borg, Åke Winqvist, R. |
author_facet |
Karppinen, S. -M. Barkardottir, R. B. Harbst, Katja Sydenham, T. Syrjakoski, K. Schleutker, J. Ikonen, T. Pylkas, 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. Moller, P. Kruse, T. A. Borg, Åke 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 |
BMJ Publishing Group |
publishDate |
2006 |
url |
https://lup.lub.lu.se/record/378323 https://doi.org/10.1136/jmg.2006.041731 |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Journal of Medical Genetics; 43(11), pp 856-862 (2006) ISSN: 0022-2593 |
op_relation |
https://lup.lub.lu.se/record/378323 http://dx.doi.org/10.1136/jmg.2006.041731 wos:000241778500004 scopus:33751242758 |
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_ |
1766041806576812032 |