RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers: Results from a combined analysis of 19 studies

Antonis C. Antoniou; Olga M. Sinilnikova; Jacques Simard; Mélanie Léoné; Martine Dumont; Susan L. Neuhausen; Jeffery P. Struewing; Dominique Stoppa-Lyonnet; Laure Barjhoux; David J. Hughes; Isabelle Coupier; Muriel Belotti; Christine Lasset; Valérie Bonadona; Yves Jean Bignon; Timothy R. Rebbeck; Theresa Wagner; Henry T. Lynch; Susan M. Domchek; Katherine L. Nathanson; Judy E. Garber; Jeffrey Weitzel; Steven A. Narod; Gail Tomlinson; Olufunmilayo I. Olopade; Andrew Godwin; Claudine Isaacs; Anna Jakubowska; Jan Lubinski; Jacek Gronwald; Bohdan Górski; Tomasz Byrski; Tomasz Huzarski; Susan Peock; Margaret Cook; Caroline Baynes; Alexandra Murray; Mark Rogers; Peter A. Daly; Huw Dorkins; Rita K. Schmutzler; Beatrix Versmold; Christoph Engel; Alfons Meindl; Norbert Arnold; Dieter Niederacher; Helmut Deissler; Amanda B. Spurdle; Xiaoqing Chen; Nicola Waddell; Nicole Cloonan; Tomas Kirchhoff; Kenneth Offit; Eitan Friedman; Bella Kaufmann; Yael Laitman; Gilli Galore; Gad Rennert; Flavio Lejbkowicz; Leon Raskin; Irene L. Andrulis; Eduard Ilyushik; Hilmi Ozcelik; Peter Devilee; Maaike P.G. Vreeswijk; Mark H. Greene; Sheila A. Prindiville; Ana Osorio; Javier Benítez; Michal Zikan; Csilla I. Szabo; Outi Kilpivaara; Heli Nevanlinna; Ute Hamann; Francine Durocher; Adalgeir Arason; Fergus J. Couch; Douglas F. Easton; Georgia Chenevix-Trench; Agnès Chompret; Brigitte Bressac-de-Paillerets; Véronique Byrde; Corinne Capoulade; Gilbert Lenoir; Nancy Uhrhammer; Marion Gauthier-Villars; Antoine De Pauw; Olga Sinilnikova; Sophie Giraud; Agnès Hardouin; Pascaline Berthet; Hagay Sobol; Violaine Bourdon; François Eisinger; Florence Coulet; Chrystelle Colas; Florent Soubrier; Jean Philippe Peyrat; Joëlle Fournier; Philippe Vennin; Claude Adenis; Catherine Nogues; Rosette Lidereau; Danièle Muller; Jean Pierre Fricker; Michel Longy; Christine Toulas; Rosine Guimbaud; Laurence Gladieff; Viviane Feillel; Dominique Leroux; Hélène Dreyfus; Christine Rebischung; Laurence Olivier-Faivre; Fabienne Prieur; Marc Frénay; Sylvie Mazoyer; Drakoulis Yannoukakos; Cassandra Engel; Neva Haites; Helen Gregory; Patrick Morrison; Trevor Cole; Carole McKeown; Alan Donaldson; Joan Paterson; Jonathon Gray; Peter Daly; David Barton; Mary Porteous; Michael Steel; Carole Brewer; Julia Rankin; Rosemarie Davidson; Victoria Murday; Louise Izatt; Gabriella Pichert; Richard Trembath; Tim Bishop; Carol Chu; Ian Ellis; Gareth Evans; Fiona Lalloo; Andrew Shenton; James Mackay; Anne Robinson; Susan Ritchie; Fiona Douglas; John Burn; Lucy Side; Sarah Durell; Ros Eeles; Jackie Cook; Oliver Quarrell; Shirley Hodgson; Diana Eccles; Anneke Lucassen

doi:10.1086/522611

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RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers: Results from a combined analysis of 19 studies

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RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers: Results from a combined analysis of 19 studies

Antonis C. Antoniou, Olga M. Sinilnikova, Jacques Simard, Mélanie Léoné, Martine Dumont, Susan L. Neuhausen, Jeffery P. Struewing, Dominique Stoppa-Lyonnet, Laure Barjhoux, David J. Hughes, …

American journal of human genetics, Vol.81(6), pp.1186-1200

2007

DOI: https://doi.org/10.1086/522611

PMCID: PMC2276351

PMID: 17999359

Abstract

Genetics

Genetics(clinical)

RAD51 is an important component of double-stranded DNA-repair mechanisms that interacts with both BRCA1 and BRCA2. A single-nucleotide polymorphism (SNP) in the 5′ untranslated region (UTR) of RAD51, 135G→C, has been suggested as a possible modifier of breast cancer risk in BRCA1 and BRCA2 mutation carriers. We pooled genotype data for 8,512 female mutation carriers from 19 studies for the RAD51 135G→C SNP. We found evidence of an increased breast cancer risk in CC homozygotes (hazard ratio [HR] 1.92 [95% confidence interval {CI} 1.25-2.94) but not in heterozygotes (HR 0.95 [95% CI 0.83-1.07]; P = .002, by heterogeneity test with 2 degrees of freedom [df]). When BRCA1 and BRCA2 mutation carriers were analyzed separately, the increased risk was statistically significant only among BRCA2 mutation carriers, in whom we observed HRs of 1.17 (95% CI 0.91-1.51) among heterozygotes and 3.18 (95% CI 1.39-7.27) among rare homozygotes (P = .007, by heterogeneity test with 2 df). In addition, we determined that the 135G→C variant affects RAD51 splicing within the 5′ UTR. Thus, 135G→C may modify the risk of breast cancer in BRCA2 mutation carriers by altering the expression of RAD51. RAD51 is the first gene to be reliably identified as a modifier of risk among BRCA1/2 mutation carriers.

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Title: RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers
Creators: Antonis C. Antoniou (Author) - University of Cambridge
Olga M. Sinilnikova (Author) - Hospices Civils de Lyon-Centre Léon Bérard;Universite Claude Bernard Lyon 1
Jacques Simard (Author) - Université Laval
Mélanie Léoné (Author) - Hospices Civils de Lyon-Centre Léon Bérard
Martine Dumont (Author) - Université Laval
Susan L. Neuhausen (Author) - University of California at Irvine
Jeffery P. Struewing (Author) - Center for Cancer Research;US NCI
Dominique Stoppa-Lyonnet (Author) - Institut Curie
Laure Barjhoux (Author) - Hospices Civils de Lyon-Centre Léon Bérard;Universite Claude Bernard Lyon 1
David J. Hughes (Author) - Trinity College Dublin
Isabelle Coupier (Author) - Institut Curie;Hôpital Arnaud de Villeneuve
Muriel Belotti (Author) - Institut Curie
Christine Lasset (Author) - Universite Claude Bernard Lyon 1;Centre Léon Bérard
Valérie Bonadona (Author) - Universite Claude Bernard Lyon 1;Centre Léon Bérard
Yves Jean Bignon (Author) - Centre Jean Perrin
Timothy R. Rebbeck (Author) - University of Pennsylvania
Theresa Wagner (Author) - Creighton University
Henry T. Lynch (Author) - Department of Preventive Medicine
Susan M. Domchek (Author) - University of Pennsylvania
Katherine L. Nathanson (Author) - University of Pennsylvania
Judy E. Garber (Author) - City of Hope National Med Center
Jeffrey Weitzel (Author) - University of Toronto
Steven A. Narod (Author) - Mount Sinai Hospital
Gail Tomlinson (Author) - University of Texas Southwestern Medical Center
Olufunmilayo I. Olopade (Author) - The University of Chicago
Andrew Godwin (Author) - University of Vienna
Claudine Isaacs (Author) - Georgetown University
Anna Jakubowska (Author) - Pomeranian Medical University in Szczecin
Jan Lubinski (Author) - Pomeranian Medical University in Szczecin
Jacek Gronwald (Author) - Pomeranian Medical University in Szczecin
Bohdan Górski (Author) - Pomeranian Medical University in Szczecin
Tomasz Byrski (Author) - Pomeranian Medical University in Szczecin
Tomasz Huzarski (Author) - Pomeranian Medical University in Szczecin
Susan Peock (Author) - University of Cambridge;Northern Ireland Regional Genetics Service
Margaret Cook (Author) - University of Cambridge;Northern Ireland Regional Genetics Service
Caroline Baynes (Author) - University of Cambridge
Alexandra Murray (Author) - University Hospital of Wales;Medical Genetics Services for Wales
Mark Rogers (Author) - University Hospital of Wales;Medical Genetics Services for Wales
Peter A. Daly (Author) - Trinity College Dublin
Huw Dorkins (Author) - Northwick Park Hospital;King's College London
Rita K. Schmutzler (Author) - University of Cologne
Beatrix Versmold (Author) - University of Cologne
Christoph Engel (Author) - Leipzig University
Alfons Meindl (Author) - Technical University of Munich
Norbert Arnold (Author) - Kiel University
Dieter Niederacher (Author) - Heinrich Heine University Düsseldorf
Helmut Deissler (Author) - Ulm University
Amanda B. Spurdle (Author) - Queensland Institute of Medical Research
Xiaoqing Chen (Author) - Queensland Institute of Medical Research
Nicola Waddell (Author) - Queensland Institute of Medical Research
Nicole Cloonan (Author) - University of Queensland
Tomas Kirchhoff (Author) - Memorial Sloan-Kettering Cancer Center
Kenneth Offit (Author) - Memorial Sloan-Kettering Cancer Center
Eitan Friedman (Author) - The Gertner Institute
Bella Kaufmann (Author) - The Gertner Institute
Yael Laitman (Author) - The Gertner Institute
Gilli Galore (Author) - The Gertner Institute
Gad Rennert (Author) - Technion-Israel Institute of Technology
Flavio Lejbkowicz (Author) - Technion-Israel Institute of Technology
Leon Raskin (Author) - Technion-Israel Institute of Technology
Irene L. Andrulis (Author) - Cancer Care Ontario;University of Texas Southwestern Medical Center
Eduard Ilyushik (Author) - Cancer Care Ontario
Hilmi Ozcelik (Author) - Cancer Care Ontario
Peter Devilee (Author) - Trinity College Dublin;Leiden University
Maaike P.G. Vreeswijk (Author) - Leiden University
Mark H. Greene (Author) - Center for Cancer Research
Sheila A. Prindiville (Author) - Center for Cancer Research;US NCI
Ana Osorio (Author) - Instituto de Salud Carlos III
Javier Benítez (Author) - Instituto de Salud Carlos III
Michal Zikan (Author) - Charles University
Csilla I. Szabo (Author) - Mayo Clinic College of Medicine and Science
Outi Kilpivaara (Author) - University of Helsinki
Heli Nevanlinna (Author) - University of Helsinki
Ute Hamann (Author) - German Cancer Research Center
Francine Durocher (Author) - Université Laval
Adalgeir Arason (Author) - Landspitali University Hospital
Fergus J. Couch (Author) - Mayo Clinic College of Medicine and Science
Douglas F. Easton (Author) - University of Cambridge
Georgia Chenevix-Trench (Author) - Ulm University
Agnès Chompret (Author) - Institut Gustave Roussy
Brigitte Bressac-de-Paillerets (Author) - Institut Gustave Roussy
Véronique Byrde (Author) - Institut Gustave Roussy
Corinne Capoulade (Author) - Institut Gustave Roussy
Gilbert Lenoir (Author) - Institut Gustave Roussy
Nancy Uhrhammer (Author) - Centre Jean Perrin
Marion Gauthier-Villars (Author) - Institut Curie
Antoine De Pauw (Author) - Institut Curie
Olga Sinilnikova (Author) - Hospices Civils de Lyon-Centre Léon Bérard
Sophie Giraud (Author) - Hospices Civils de Lyon-Centre Léon Bérard
Agnès Hardouin (Author) - Centre Georges-François Leclerc
Pascaline Berthet (Author) - Centre Georges-François Leclerc
Hagay Sobol (Author) - Institut Paoli Calmettes
Violaine Bourdon (Author) - Institut Paoli Calmettes
François Eisinger (Author) - Institut Paoli Calmettes
Florence Coulet (Author) - Sorbonne Université
Chrystelle Colas (Author) - Sorbonne Université
Florent Soubrier (Author) - Sorbonne Université
Jean Philippe Peyrat (Author) - Centre Oscar Lambret
Joëlle Fournier (Author) - Centre Oscar Lambret
Philippe Vennin (Author) - Centre Oscar Lambret
Claude Adenis (Author) - Centre Oscar Lambret
Catherine Nogues (Author) - Centre René Huguenin
Rosette Lidereau (Author) - Centre René Huguenin
Danièle Muller (Author) - Centre Georges-François Leclerc
Jean Pierre Fricker (Author) - Centre Georges-François Leclerc
Michel Longy (Author) - Centre Georges-François Leclerc
Christine Toulas (Author) - Institut Claudius Regaud
Rosine Guimbaud (Author) - Institut Claudius Regaud
Laurence Gladieff (Author) - Institut Claudius Regaud
Viviane Feillel (Author) - Institut Claudius Regaud
Dominique Leroux (Author) - Universite Joseph Fourier
Hélène Dreyfus (Author) - Universite Joseph Fourier
Christine Rebischung (Author) - Universite Joseph Fourier
Laurence Olivier-Faivre (Author) - Université de Bourgogne
Fabienne Prieur (Author) - CHU de Saint-Étienne
Marc Frénay (Author) - Centre Antoine Lacassagne
Sylvie Mazoyer (Author) - CNRS
Drakoulis Yannoukakos (Author) - Demokritos National Centre for Scientific Research
Cassandra Engel (Author) - Coordinating Centre
Neva Haites (Author) - North of Scotland Regional Genetics Service
Helen Gregory (Author) - North of Scotland Regional Genetics Service
Patrick Morrison (Author) - Northern Ireland Regional Genetics Service
Trevor Cole (Author) - West Midlands Regional Clinical Genetics Service
Carole McKeown (Author) - West Midlands Regional Clinical Genetics Service
Alan Donaldson (Author) - South West Regional Genetics Service
Joan Paterson (Author) - East Anglian Regional Genetics Service
Jonathon Gray (Author) - Medical Genetics Services for Wales
Peter Daly (Author) - Trinity College Dublin
David Barton (Author) - National Centre for Medical Genetics
Mary Porteous (Author) - South East of Scotland Regional Genetics Service
Michael Steel (Author) - South East of Scotland Regional Genetics Service
Carole Brewer (Author) - Peninsula Clinical Genetics Service
Julia Rankin (Author) - Peninsula Clinical Genetics Service
Rosemarie Davidson (Author) - West of Scotland Regional Genetics Service
Victoria Murday (Author) - West of Scotland Regional Genetics Service
Louise Izatt (Author) - King's College London
Gabriella Pichert (Author) - North West Thames Regional Genetics Service
Richard Trembath (Author) - Leicestershire Clinical Genetics Service
Tim Bishop (Author) - Yorkshire Regional Genetics Service
Carol Chu (Author) - Yorkshire Regional Genetics Service
Ian Ellis (Author) - Cheshire and Merseyside Clinical Genetics Service
Gareth Evans (Author) - Manchester Regional Genetics Service
Fiona Lalloo (Author) - Manchester Regional Genetics Service
Andrew Shenton (Author) - Manchester Regional Genetics Service
James Mackay (Author) - North East Thames Regional Genetics Service
Anne Robinson (Author) - North East Thames Regional Genetics Service
Susan Ritchie (Author) - Nottingham University Hospitals NHS Trust
Fiona Douglas (Author) - Northern Clinical Genetics Service
John Burn (Author) - Northern Clinical Genetics Service
Lucy Side (Author) - Oxford Regional Genetics Service
Sarah Durell (Author) - Oxford Regional Genetics Service
Ros Eeles (Author) - Royal Marsden Hospital
Jackie Cook (Author) - Sheffield Clinical Genetics Service
Oliver Quarrell (Author) - Sheffield Clinical Genetics Service
Shirley Hodgson (Author) - SouthWest Thames Regional Genetics Service
Diana Eccles (Author) - Wessex Clinical Genetics Service
Anneke Lucassen (Author) - Wessex Clinical Genetics Service
Publication Details: American journal of human genetics, Vol.81(6), pp.1186-1200
Series: 81
Number of pages: 15
Identifiers: 991005929587502656
Academic Unit: Prev. Medicine & Public Health
Language: English
Resource Type: Journal article