The BARD1 Cys557Ser variant and breast cancer risk in Iceland.
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field BACKGROUND: Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-...
Published in: | PLoS Medicine |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , |
Other Authors: | |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science
2009
|
Subjects: | |
Online Access: | http://hdl.handle.net/2336/65453 https://doi.org/10.1371/journal.pmed.0030217 |
id |
ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/65453 |
---|---|
record_format |
openpolar |
spelling |
ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/65453 2023-05-15T16:50:01+02:00 The BARD1 Cys557Ser variant and breast cancer risk in Iceland. Stacey, Simon N Sulem, Patrick Johannsson, Oskar T Helgason, Agnar Gudmundsson, Julius Kostic, Jelena P Kristjansson, Kristleifur Jonsdottir, Thora Sigurdsson, Helgi Hrafnkelsson, Jon Johannsson, Jakob Sveinsson, Thorarinn Myrdal, Gardar Grimsson, Hlynur Niels Bergthorsson, Jon T Amundadottir, Laufey T Gulcher, Jeffrey R Thorsteinsdottir, Unnur Kong, Augustine Stefansson, Kari deCODE Genetics, Reykjavik, Iceland. simon.stacey@decode.is 2009-04-20 http://hdl.handle.net/2336/65453 https://doi.org/10.1371/journal.pmed.0030217 en eng Public Library of Science http://dx.doi.org/10.1371%2Fjournal.pmed.0030217 PLoS Med. 2006, 3(7):e217 1549-1676 16768547 doi:10.1371/journal.pmed.0030217 http://hdl.handle.net/2336/65453 PLoS medicine Adult Age of Onset Aged Alleles Amino Acid Substitution Breast Neoplasms Carcinoma in Situ Carcinoma Ductal Breast Intraductal Noninfiltrating Lobular Medullary Case-Control Studies Cluster Analysis Cohort Studies Female Founder Effect Gene Frequency Genes BRCA2 Genetic Predisposition to Disease Genotype Haplotypes Humans Iceland Middle Aged Mutation Missense Neoplastic Syndromes Hereditary Odds Ratio Point Mutation Polymorphism Single Nucleotide Risk Sequence Deletion Tumor Suppressor Proteins Ubiquitin-Protein Ligases Article 2009 ftlandspitaliuni https://doi.org/10.1371/journal.pmed.0030217 2022-05-29T08:21:18Z To access publisher full text version of this article. Please click on the hyperlink in Additional Links field BACKGROUND: Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer. METHODS AND FINDINGS: The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11-3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22-4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16-8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas ... Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive PLoS Medicine 3 7 e217 |
institution |
Open Polar |
collection |
Hirsla - Landspítali University Hospital research archive |
op_collection_id |
ftlandspitaliuni |
language |
English |
topic |
Adult Age of Onset Aged Alleles Amino Acid Substitution Breast Neoplasms Carcinoma in Situ Carcinoma Ductal Breast Intraductal Noninfiltrating Lobular Medullary Case-Control Studies Cluster Analysis Cohort Studies Female Founder Effect Gene Frequency Genes BRCA2 Genetic Predisposition to Disease Genotype Haplotypes Humans Iceland Middle Aged Mutation Missense Neoplastic Syndromes Hereditary Odds Ratio Point Mutation Polymorphism Single Nucleotide Risk Sequence Deletion Tumor Suppressor Proteins Ubiquitin-Protein Ligases |
spellingShingle |
Adult Age of Onset Aged Alleles Amino Acid Substitution Breast Neoplasms Carcinoma in Situ Carcinoma Ductal Breast Intraductal Noninfiltrating Lobular Medullary Case-Control Studies Cluster Analysis Cohort Studies Female Founder Effect Gene Frequency Genes BRCA2 Genetic Predisposition to Disease Genotype Haplotypes Humans Iceland Middle Aged Mutation Missense Neoplastic Syndromes Hereditary Odds Ratio Point Mutation Polymorphism Single Nucleotide Risk Sequence Deletion Tumor Suppressor Proteins Ubiquitin-Protein Ligases Stacey, Simon N Sulem, Patrick Johannsson, Oskar T Helgason, Agnar Gudmundsson, Julius Kostic, Jelena P Kristjansson, Kristleifur Jonsdottir, Thora Sigurdsson, Helgi Hrafnkelsson, Jon Johannsson, Jakob Sveinsson, Thorarinn Myrdal, Gardar Grimsson, Hlynur Niels Bergthorsson, Jon T Amundadottir, Laufey T Gulcher, Jeffrey R Thorsteinsdottir, Unnur Kong, Augustine Stefansson, Kari The BARD1 Cys557Ser variant and breast cancer risk in Iceland. |
topic_facet |
Adult Age of Onset Aged Alleles Amino Acid Substitution Breast Neoplasms Carcinoma in Situ Carcinoma Ductal Breast Intraductal Noninfiltrating Lobular Medullary Case-Control Studies Cluster Analysis Cohort Studies Female Founder Effect Gene Frequency Genes BRCA2 Genetic Predisposition to Disease Genotype Haplotypes Humans Iceland Middle Aged Mutation Missense Neoplastic Syndromes Hereditary Odds Ratio Point Mutation Polymorphism Single Nucleotide Risk Sequence Deletion 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: Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer. METHODS AND FINDINGS: The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11-3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22-4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16-8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas ... |
author2 |
deCODE Genetics, Reykjavik, Iceland. simon.stacey@decode.is |
format |
Article in Journal/Newspaper |
author |
Stacey, Simon N Sulem, Patrick Johannsson, Oskar T Helgason, Agnar Gudmundsson, Julius Kostic, Jelena P Kristjansson, Kristleifur Jonsdottir, Thora Sigurdsson, Helgi Hrafnkelsson, Jon Johannsson, Jakob Sveinsson, Thorarinn Myrdal, Gardar Grimsson, Hlynur Niels Bergthorsson, Jon T Amundadottir, Laufey T Gulcher, Jeffrey R Thorsteinsdottir, Unnur Kong, Augustine Stefansson, Kari |
author_facet |
Stacey, Simon N Sulem, Patrick Johannsson, Oskar T Helgason, Agnar Gudmundsson, Julius Kostic, Jelena P Kristjansson, Kristleifur Jonsdottir, Thora Sigurdsson, Helgi Hrafnkelsson, Jon Johannsson, Jakob Sveinsson, Thorarinn Myrdal, Gardar Grimsson, Hlynur Niels Bergthorsson, Jon T Amundadottir, Laufey T Gulcher, Jeffrey R Thorsteinsdottir, Unnur Kong, Augustine Stefansson, Kari |
author_sort |
Stacey, Simon N |
title |
The BARD1 Cys557Ser variant and breast cancer risk in Iceland. |
title_short |
The BARD1 Cys557Ser variant and breast cancer risk in Iceland. |
title_full |
The BARD1 Cys557Ser variant and breast cancer risk in Iceland. |
title_fullStr |
The BARD1 Cys557Ser variant and breast cancer risk in Iceland. |
title_full_unstemmed |
The BARD1 Cys557Ser variant and breast cancer risk in Iceland. |
title_sort |
bard1 cys557ser variant and breast cancer risk in iceland. |
publisher |
Public Library of Science |
publishDate |
2009 |
url |
http://hdl.handle.net/2336/65453 https://doi.org/10.1371/journal.pmed.0030217 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://dx.doi.org/10.1371%2Fjournal.pmed.0030217 PLoS Med. 2006, 3(7):e217 1549-1676 16768547 doi:10.1371/journal.pmed.0030217 http://hdl.handle.net/2336/65453 PLoS medicine |
op_doi |
https://doi.org/10.1371/journal.pmed.0030217 |
container_title |
PLoS Medicine |
container_volume |
3 |
container_issue |
7 |
container_start_page |
e217 |
_version_ |
1766040196201054208 |