Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers

Susan J Ramus; Christiana Kartsonaki; Simon A Gayther; Paul D P Pharoah; Olga M Sinilnikova; Jonathan Beesley; Xiaoqing Chen; Lesley McGuffog; Sue Healey; Fergus J Couch; Xianshu Wang; Zachary Fredericksen; Paolo Peterlongo; Siranoush Manoukian; Bernard Peissel; Daniela Zaffaroni; Gaia Roversi; Monica Barile; Alessandra Viel; Anna Allavena; Laura Ottini; Laura Papi; Viviana Gismondi; Fabio Capra; Paolo Radice; Mark H Greene; Phuong L Mai; Irene L Andrulis; Gord Glendon; Hilmi Ozcelik; Mads Thomassen; Anne-Marie Gerdes; Torben A Kruse; Dorthe Cruger; Uffe Birk Jensen; Maria Adelaide Caligo; Hakan Olsson; Annika Lindblom; Brita Arver; Per Karlsson; Marie Stenmark Askmalm; Ake Borg; Susan L Neuhausen; Yuan Chun Ding; Katherine L Nathanson; Susan M Domchek; Anna Jakubowska; Jan Lubinski; Tomasz Huzarski; Tomasz Byrski; Jacek Gronwald; Bohdan Gorski; Cezary Cybulski; Tadeusz Debniak; Ana Osorio; Maria-Isabel Tejada; Javier Benitez; Ute Hamann; Matti A Rookus; Senno Verhoef; Madeleine A Tilanus-Linthorst; Maaike P Vreeswijk; Danielle Bodmer; Margreet G E M Ausems; Theo A van Os; Christi J Asperen; Marinus J Blok; Hanne E J Meijers-Heijboer; Susan Peock; Margaret Cook; Clare Oliver; Debra Frost; Alison M Dunning; D Gareth Evans; Ros Eeles; Trevor Cole; Shirley Hodgson; Patrick J Morrison; Mary Porteous; M John Kennedy; Mark T Rogers; Lucy E Side; Alan Donaldson; Helen Gregory; Andrew Godwin; Virginie Moncoutier; Laurent Castera; Sylvie Mazoyer; Valerie Bonadona; Dominique Leroux; Laurence Faivre; Rosette Lidereau; Catherine Nogues; Yves-Jean Bignon; Fabienne Prieur; Marie-Agnes Collonge-Rame; Laurence Venat-Bouvet; Sandra Fert-Ferrer; Alex Miron; Saundra S Buys; John L Hopper; Mary B Daly; Esther M John; Mary Beth Terry; David Goldgar; Thomas V O Hansen; Lars Jonson; Bent Ejlertsen; Bjarni A Agnarsson; Kenneth Offit; Tomas Kirchhoff; Joseph Vijai; Ana V C Dutra-Clarke; Jennifer A Przybylo; Marco Montagna; Cinzia Casella; Evgeny N Imyanitov; Ramunas Janavicius; Ignacio Blanco; Conxi Lazaro; Kirsten B Moysich; Beth Y Karlan; Jenny Gross; Rita Schmutzler; Barbara Wappenschmidt; Alfons Meindl; Britta Fiebig; Christian Sutter; Norbert Arnold; Helmut Deissler; Raymonda Varon-Mateeva; Karin Kast; Dieter Niederacher; Dorothea Gadzicki; Trinidad Caldes; Heli Nevanlinna; Kristiina Aittomaeki; Jacques Simard; Penny Soucy; Amanda B Spurdle; Helene Holland; Georgia Chenevix-Trench; Douglas F Easton; Antonis C Antoniou; KConFab Investigators; Christine June Jacobs

doi:10.1093/jnci/djq494

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Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers

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Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers

Susan J Ramus, Christiana Kartsonaki, Simon A Gayther, Paul D P Pharoah, Olga M Sinilnikova, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Sue Healey, Fergus J Couch, …

JNCI : Journal of the National Cancer Institute, Vol.103(2), pp.105-116

19/01/2011

DOI: https://doi.org/10.1093/jnci/djq494

PMID: 21169536

Abstract

TECHNOLOGY

TEKNIKVETENSKAP

Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. Methods We genotyped rs3814113 in 10 029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. Results The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 x 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 x 10(-4)). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. Conclusion Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation.

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Title: Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers
Creators: Susan J Ramus - University College London
Christiana Kartsonaki - University of Cambridge
Simon A Gayther - UCL, Department Gynaecol Oncol, UCL EGA Institute Womens Hlth, London, England
Paul D P Pharoah - University of Cambridge
Olga M Sinilnikova - Centre Léon Bérard
Jonathan Beesley - QIMR Berghofer Medical Research Institute
Xiaoqing Chen - QIMR Berghofer Medical Research Institute
Lesley McGuffog - University of Cambridge
Sue Healey - QIMR Berghofer Medical Research Institute
Fergus J Couch - College Station Medical Center
Xianshu Wang - College Station Medical Center
Zachary Fredericksen - WinnMed
Paolo Peterlongo - Mylan
Siranoush Manoukian - Université Claude Bernard Lyon 1
Bernard Peissel - Predict
Daniela Zaffaroni - Predict
Gaia Roversi - Predict
Monica Barile - Mylan
Alessandra Viel - Czech Radio
Anna Allavena - European Institute of Oncology
Laura Ottini - College Station Medical Center
Laura Papi - University of Turin
Viviana Gismondi - Genoa
Fabio Capra - University of Florence
Paolo Radice - University College London
Mark H Greene - NCI, Div Canc Epidemiol and Genet, Clin Genet Branch, Bethesda, MD 20892 USA
Phuong L Mai - NCI, Div Canc Epidemiol and Genet, Clin Genet Branch, Bethesda, MD 20892 USA
Irene L Andrulis - Lunenfeld-Tanenbaum Research Institute
Gord Glendon - National Institutes of Health
Hilmi Ozcelik - University of Toronto
Mads Thomassen - Cancer Care Ontario
Anne-Marie Gerdes - Odense University Hospital
Torben A Kruse - Odense University Hospital
Dorthe Cruger - University of Southern Denmark
Uffe Birk Jensen - Aarhus University Hospital
Maria Adelaide Caligo - University Hospital Pisa, Department Oncol, Sect Genet Oncol, Pisa, Italy
Hakan Olsson - Lund University
Annika Lindblom - Aarhus University
Brita Arver - University of Pisa
Per Karlsson - Lund University
Marie Stenmark Askmalm - Klinisk patologi och klinisk genetik
Ake Borg - Lund University
Susan L Neuhausen - Beckman Research Institute
Yuan Chun Ding - Beckman Research Institute
Katherine L Nathanson - Supreme Council Of Health
Susan M Domchek - Supreme Council Of Health
Anna Jakubowska - University of Gothenburg
Jan Lubinski - University of Gothenburg
Tomasz Huzarski - University of Gothenburg
Tomasz Byrski - University of Gothenburg
Jacek Gronwald - University of Gothenburg
Bohdan Gorski - University of Gothenburg
Cezary Cybulski - University of Gothenburg
Tadeusz Debniak - College Station Medical Center
Ana Osorio - Linköping University
Maria-Isabel Tejada - Cruces Hospital Barakaldo, Mol Genet Lab, Department Biochem, Bizkaia, Spain
Javier Benitez - Pomeranian Medical University
Ute Hamann - Heidelberg
Matti A Rookus - Netherlands Canc Institute, Department Epidemiol, Amsterdam, Netherlands
Senno Verhoef - Netherlands Canc Institute, Family Canc Clin, Amsterdam, Netherlands
Madeleine A Tilanus-Linthorst - Erasmus MC
Maaike P Vreeswijk - Leiden University
Danielle Bodmer - Radboud University Nijmegen
Margreet G E M Ausems - College Station Medical Center
Theo A van Os - University of Amsterdam
Christi J Asperen - Leiden University
Marinus J Blok - University Hospital Maastricht, Department Clin Genet, Maastricht, Netherlands
Hanne E J Meijers-Heijboer - University of Amsterdam
Susan Peock - Amsterdam University of the Arts
Margaret Cook - Maastricht University
Clare Oliver - Vrije Universiteit Amsterdam
Debra Frost - University of Cambridge
Alison M Dunning - University of Cambridge
D Gareth Evans - Cent Manchester University Hospital NHS Fdn Trust, Manchester Acad Hlth Science Centre, Manchester, Lancs England
Ros Eeles - Guys and St Thomas NHS Fdn Trust, London, England
Trevor Cole - University of London
Shirley Hodgson - Royal Devon and Exeter Hospital
Patrick J Morrison - Belfast City Hospital
Mary Porteous - Trinity College Dublin
M John Kennedy - Trinity Coll Dublin, Acad Unit Clin and Mol Oncol, Dublin, Eire Ireland St James Hospital, Dublin, Eire Ireland
Mark T Rogers - University of Wales
Lucy E Side - Ormond
Alan Donaldson - University of Aberdeen
Helen Gregory - Fox Chase Cancer Center
Andrew Godwin - Université Paris Cité
Virginie Moncoutier - Université Claude Bernard Lyon 1
Laurent Castera - Université Joseph Fourier
Sylvie Mazoyer - Université de Bourgogne
Valerie Bonadona - Centre Léon Bérard
Dominique Leroux - Laboratoire de Biométrie et Biologie Evolutive
Laurence Faivre - Université de Bourgogne
Rosette Lidereau - Université de franche-comté
Catherine Nogues - Centre Rene Huguenin, Epidemiol Clin, St Cloud, France
Yves-Jean Bignon - Centre Jean Perrin
Fabienne Prieur - Harvard University Press
Marie-Agnes Collonge-Rame - Charmo University
Laurence Venat-Bouvet - University of Melbourne
Sandra Fert-Ferrer - Hotel Dieu Centre Hospital, Lab Genet Chromosom, Chambery, France
Alex Miron - Ludwig-Maximilians-Universität München
Saundra S Buys - University of Utah
John L Hopper - University of Melbourne
Mary B Daly - College Station Medical Center
Esther M John - Stanford University
Mary Beth Terry - Columbia University
David Goldgar - University of Utah
Thomas V O Hansen - Copenhagen University Hospital
Lars Jonson - Copenhagen University Hospital
Bent Ejlertsen - Roswell Park Comprehensive Cancer Center
Bjarni A Agnarsson - University of Iceland
Kenneth Offit - University of California, San Francisco
Tomas Kirchhoff - Mécanique et Engrenage Moderne
Joseph Vijai - University of Cologne
Ana V C Dutra-Clarke - Mécanique et Engrenage Moderne
Jennifer A Przybylo - Mécanique et Engrenage Moderne
Marco Montagna - University of Regensburg
Cinzia Casella - Heidelberg University
Evgeny N Imyanitov - NN Petrov Institute Oncol, St Petersburg, Russia
Ramunas Janavicius - Universität Ulm
Ignacio Blanco - Charité - Universitätsmedizin Berlin
Conxi Lazaro - TU Dresden
Kirsten B Moysich - Roswell Pk Canc Institute, Department Canc Prevent and Control, Buffalo, NY 14263 USA
Beth Y Karlan - College Station Medical Center
Jenny Gross - Universidad Complutense de Madrid
Rita Schmutzler - University of Helsinki
Barbara Wappenschmidt - Université Laval
Alfons Meindl - University of Cambridge
Britta Fiebig - University College London
Christian Sutter - University of Cambridge
Norbert Arnold - University of Cambridge
Helmut Deissler - University Hospital Ulm
Raymonda Varon-Mateeva - Mayo Clinic
Karin Kast - WinnMed
Dieter Niederacher - University of Cambridge
Dorothea Gadzicki - QIMR Berghofer Medical Research Institute
Trinidad Caldes - QIMR Berghofer Medical Research Institute
Heli Nevanlinna - University of Helsinki
Kristiina Aittomaeki - University of Helsinki
Jacques Simard - University College London
Penny Soucy - University College London
Amanda B Spurdle - College Station Medical Center
Helene Holland - College Station Medical Center
Georgia Chenevix-Trench - College Station Medical Center
Douglas F Easton - University of Cambridge
Antonis C Antoniou - University of Cambridge
KConFab Investigators
Christine June Jacobs - School of Health Sciences
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.103(2), pp.105-116
Date published: 19/01/2011
Identifiers: 99928679502346
Academic Unit: School of Health Sciences
Language: English
Resource Type: Journal article

Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers

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