Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

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

Author:
  • S. -M. Karppinen
  • R. B. Barkardottir
  • Katja Harbst
  • T. Sydenham
  • K. Syrjakoski
  • J. Schleutker
  • T. Ikonen
  • K. Pylkas
  • K. Rapakko
  • H. Erkko
  • G. Johannesdottir
  • A. -M. Gerdes
  • M. Thomassen
  • B. A. Agnarsson
  • M. Grip
  • A. Kallioniemi
  • J. Kere
  • L. A. Aaltonen
  • A. Arason
  • P. Moller
  • T. A. Kruse
  • Åke Borg
  • R. Winqvist
Publishing year: 2006
Language: English
Pages: 856-862
Publication/Series: Journal of Medical Genetics
Volume: 43
Issue: 11
Document type: Journal article
Publisher: BMJ Publishing Group

Abstract english

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.

Keywords

  • Medical Genetics

Other

Published
  • ISSN: 0022-2593
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90