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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 LU orcid ; Sydenham, T. ; Syrjakoski, K. ; Schleutker, J. ; Ikonen, T. ; Pylkas, K. ; Rapakko, K. and Erkko, H. , et al. (2006) In Journal of Medical Genetics 43(11). p.856-862
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medical Genetics
volume
43
issue
11
pages
856 - 862
publisher
BMJ Publishing Group
external identifiers
  • wos:000241778500004
  • scopus:33751242758
ISSN
0022-2593
DOI
10.1136/jmg.2006.041731
language
English
LU publication?
yes
id
14637813-bd56-47a5-8610-60ad65b0803e (old id 378323)
date added to LUP
2016-04-01 15:54:13
date last changed
2021-01-06 08:38:22
@article{14637813-bd56-47a5-8610-60ad65b0803e,
  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 &lt; 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.},
  author       = {Karppinen, S. -M. and Barkardottir, R. B. and Harbst, Katja and Sydenham, T. and Syrjakoski, K. and Schleutker, J. and Ikonen, T. and Pylkas, K. and Rapakko, K. and Erkko, H. and Johannesdottir, G. and Gerdes, A. -M. and Thomassen, M. and Agnarsson, B. A. and Grip, M. and Kallioniemi, A. and Kere, J. and Aaltonen, L. A. and Arason, A. and Moller, P. and Kruse, T. A. and Borg, Åke and Winqvist, R.},
  issn         = {0022-2593},
  language     = {eng},
  number       = {11},
  pages        = {856--862},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Medical Genetics},
  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},
  url          = {http://dx.doi.org/10.1136/jmg.2006.041731},
  doi          = {10.1136/jmg.2006.041731},
  volume       = {43},
  year         = {2006},
}