Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Antonis C. Antoniou; Jonathan Beesley; Lesley McGuffog; Olga M. Sinilnikova; Sue Healey; Susan L. Neuhausen; Yuan Chun Ding; Timothy R. Rebbeck; Jeffrey N. Weitzel; Henry T. Lynch; Claudine Isaacs; Patricia A. Ganz; Gail Tomlinson; Olufunmilayo I. Olopade; Fergus J. Couch; Xianshu Wang; Noralane M. Lindor; Vernon S. Pankratz; Paolo Radice; Siranoush Manoukian; Bernard Peissel; Daniela Zaffaroni; Monica Barile; Alessandra Viel; Anna Allavena; Valentina Dall'Olio; Paolo Peterlongo; Csilla I. Szabo; Michal Zikan; Kathleen Claes; Bruce Poppe; Lenka Foretova; Phuong L. Mai; Mark H. Greene; Gad Rennert; Flavio Lejbkowicz; Gord Glendon; Hilmi Ozcelik; Irene L. Andrulis; Mads Thomassen; Anne-Marie Gerdes; Lone Sunde; Dorthe Cruger; Uffe Birk Jensen; Maria Caligo; Eitan Friedman; Bella Kaufman; Yael Laitman; Roni Milgrom; Maya Dubrovsky; Shimrit Cohen; Ake Borg; Helena Jernstroem; Annika Lindblom; Johanna Rantala; Marie Stenmark-Askmalm; Beatrice Melin; Kate Nathanson; Susan Domchek; Ania Jakubowska; Jan Lubinski; Tomasz Huzarski; Ana Osorio; Adriana Lasa; Mercedes Duran; Maria-Isabel Tejada; Javier Godino; Javier Benitez; Ute Hamann; Mieke Kriege; Nicoline Hoogerbrugge; Rob B. van der Luijt; Christi J. van Asperen; Peter Devilee; E. J. Meijers-Heijboer; Marinus J. Blok; Cora M. Aalfs; Frans Hogervorst; Matti Rookus; Margaret Cook; Clare Oliver; Debra Frost; Don Conroy; D. Gareth Evans; Fiona Lalloo; Gabriella Pichert; Rosemarie Davidson; Trevor Cole; Jackie Cook; Joan Paterson; Shirley Hodgson; Patrick J. Morrison; Mary E. Porteous; Lisa Walker; M. John Kennedy; Huw Dorkins; Susan Peock; Andrew K. Godwin; Dominique Stoppa-Lyonnet; Antoine de Pauw; Ontario Canc Genetics Network; Christine June Jacobs

doi:10.1158/0008-5472.CAN-10-1907

Back

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Journal article

Open access

Peer reviewed

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Antonis C. Antoniou, Jonathan Beesley, Lesley McGuffog, Olga M. Sinilnikova, Sue Healey, Susan L. Neuhausen, Yuan Chun Ding, Timothy R. Rebbeck, Jeffrey N. Weitzel, Henry T. Lynch, …

Cancer research (Chicago, Ill.), Vol.70(23), pp.9742-9754

01/12/2010

DOI: https://doi.org/10.1158/0008-5472.CAN-10-1907

PMID: 21118973

Abstract

Life Sciences & Biomedicine

Oncology

Science & Technology

The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR - 1.10, 95% CI: 1.03-1.18, P - 0.006 and HR - 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P 7 = 10 x (11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42%

Files and links (1)

url

https://doi.org/10.1158/0008-5472.CAN-10-1907View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction
Creators: Antonis C. Antoniou - Georgetown University
Jonathan Beesley - Georgetown University
Lesley McGuffog - Georgetown University
Olga M. Sinilnikova - Centre Léon Bérard
Sue Healey - QIMR Berghofer Medical Research Institute
Susan L. Neuhausen - City of Hope
Yuan Chun Ding - City of Hope
Timothy R. Rebbeck - Georgetown University
Jeffrey N. Weitzel - City of Hope
Henry T. Lynch - Georgetown University
Claudine Isaacs - Georgetown University
Patricia A. Ganz - Georgetown University
Gail Tomlinson - Georgetown University
Olufunmilayo I. Olopade - Georgetown University
Fergus J. Couch - Georgetown University
Xianshu Wang - Georgetown University
Noralane M. Lindor - Georgetown University
Vernon S. Pankratz - Centre Léon Bérard
Paolo Radice - Georgetown University
Siranoush Manoukian - Georgetown University
Bernard Peissel - Georgetown University
Daniela Zaffaroni - Centre Léon Bérard
Monica Barile - Georgetown University
Alessandra Viel - Czech Radio
Anna Allavena - Georgetown University
Valentina Dall'Olio - Cogentech, Consortium Genom Technol, Milan, Italy
Paolo Peterlongo - Georgetown University
Csilla I. Szabo - Georgetown University
Michal Zikan - Georgetown University
Kathleen Claes - Georgetown University
Bruce Poppe - Georgetown University
Lenka Foretova - Georgetown University
Phuong L. Mai - US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA
Mark H. Greene - Georgetown University
Gad Rennert - Georgetown University
Flavio Lejbkowicz - Georgetown University
Gord Glendon - Georgetown University
Hilmi Ozcelik - Georgetown University
Irene L. Andrulis - Georgetown University
Mads Thomassen - Georgetown University
Anne-Marie Gerdes - Rigshosp, Dept Clin Genet, Odense, Denmark
Lone Sunde - Georgetown University
Dorthe Cruger - Georgetown University
Uffe Birk Jensen - Georgetown University
Maria Caligo - Georgetown University
Eitan Friedman - Georgetown University
Bella Kaufman - Georgetown University
Yael Laitman - Georgetown University
Roni Milgrom - Georgetown University
Maya Dubrovsky - QIMR Berghofer Medical Research Institute
Shimrit Cohen - Georgetown University
Ake Borg - Georgetown University
Helena Jernstroem - Lund University
Annika Lindblom - Georgetown University
Johanna Rantala - Centre Léon Bérard
Marie Stenmark-Askmalm - Georgetown University
Beatrice Melin - Georgetown University
Kate Nathanson - Univ Penn, Philadelphia, PA 19104 USA
Susan Domchek - Georgetown University
Ania Jakubowska - College Station Medical Center
Jan Lubinski - Centre Léon Bérard
Tomasz Huzarski - City Of Hope National Medical Center
Ana Osorio - Georgetown University
Adriana Lasa - Georgetown University
Mercedes Duran - Georgetown University
Maria-Isabel Tejada - Cruces Hosp Barakaldo, Mol Genet Lab, Dept Biochem, Bizkaia, Spain
Javier Godino - Georgetown University
Javier Benitez - Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain
Ute Hamann - Georgetown University
Mieke Kriege - Georgetown University
Nicoline Hoogerbrugge - Georgetown University
Rob B. van der Luijt - Georgetown University
Christi J. van Asperen - Georgetown University
Peter Devilee - Georgetown University
E. J. Meijers-Heijboer - Georgetown University
Marinus J. Blok - Centre Léon Bérard
Cora M. Aalfs - Georgetown University
Frans Hogervorst - Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands
Matti Rookus - Georgetown University
Margaret Cook - Georgetown University
Clare Oliver - Georgetown University
Debra Frost - Georgetown University
Don Conroy - Georgetown University
D. Gareth Evans - Georgetown University
Fiona Lalloo - Georgetown University
Gabriella Pichert - Georgetown University
Rosemarie Davidson - Georgetown University
Trevor Cole - Georgetown University
Jackie Cook - Centre Léon Bérard
Joan Paterson - QIMR Berghofer Medical Research Institute
Shirley Hodgson - Centre Léon Bérard
Patrick J. Morrison - Georgetown University
Mary E. Porteous - Centre Léon Bérard
Lisa Walker - Georgetown University
M. John Kennedy - Georgetown University
Huw Dorkins - Georgetown University
Susan Peock - Georgetown University
Andrew K. Godwin - Georgetown University
Dominique Stoppa-Lyonnet - Univ Paris 05, INSERM, U509, Serv Genet Oncol,Inst Curie, Paris, France
Antoine de Pauw - Centre Léon Bérard
Ontario Canc Genetics Network
Christine June Jacobs - School of Health Sciences
Publication Details: Cancer research (Chicago, Ill.), Vol.70(23), pp.9742-9754
Publisher: Amer Assoc Cancer Research
Number of pages: 13
Date published: 01/12/2010
Grant note: 11174 / Cancer Research UK Cancer Research UK Associazione Italiana per la Ricerca sul Cancro; Fondazione AIRC per la ricerca sul cancro N01CP011019 / DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics U01CA069467 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
Identifiers: 99928922302346
Academic Unit: School of Health Sciences
Language: English
Resource Type: Journal article

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Abstract

Files and links (1)

Metrics

Details

Usage Policy