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Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Journal article
Authors Susan J Ramus
Antonis C Antoniou
Karoline B Kuchenbaecker
Penny Soucy
Jonathan Beesley
Xiaoqing Chen
Lesley McGuffog
Olga M Sinilnikova
Sue Healey
Daniel Barrowdale
Andrew Lee
Mads Thomassen
Anne-Marie Gerdes
Torben A Kruse
Uffe Birk Jensen
Anne-Bine Skytte
Maria A Caligo
Annelie Liljegren
Annika Lindblom
Håkan Olsson
Ulf Kristoffersson
Marie Stenmark-Askmalm
Beatrice Melin
Zakaria Einbeigi
Susan M Domchek
Katherine L Nathanson
Timothy R Rebbeck
Anna Jakubowska
Jan Lubinski
Katarzyna Jaworska
Katarzyna Durda
Elżbieta Złowocka
Jacek Gronwald
Tomasz Huzarski
Tomasz Byrski
Cezary Cybulski
Aleksandra Toloczko-Grabarek
Ana Osorio
Javier Benitez
Mercedes Duran
Maria-Isabel Tejada
Ute Hamann
Matti Rookus
Flora E van Leeuwen
Cora M Aalfs
Hanne E J Meijers-Heijboer
Christi J van Asperen
K E P van Roozendaal
Nicoline Hoogerbrugge
J Margriet Collée
Mieke Kriege
Rob B van der Luijt
Susan Peock
Debra Frost
Steve D Ellis
Radka Platte
Elena Fineberg
D Gareth Evans
Fiona Lalloo
Chris Jacobs
Joan Paterson
Fiona Douglas
Carole Brewer
Shirley Hodgson
Patrick J Morrison
Lisa Walker
Mary E Porteous
M John Kennedy
Harsh Pathak
Andrew K Godwin
Dominique Stoppa-Lyonnet
Virginie Caux-Moncoutier
Antoine de Pauw
Marion Gauthier-Villars
Sylvie Mazoyer
Mélanie Léoné
Alain Calender
Christine Lasset
Valérie Bonadona
Agnès Hardouin
Pascaline Berthet
Yves-Jean Bignon
Nancy Uhrhammer
Laurence Faivre
Catherine Loustalot
Saundra Buys
Mary Daly
Alex Miron
Mary Beth Terry
Wendy K Chung
Esther M John
Melissa Southey
David Goldgar
Christian F Singer
Muy-Kheng Tea
Georg Pfeiler
Anneliese Fink-Retter
Thomas V O Hansen
Bent Ejlertsen
Oskar Th Johannsson
Kenneth Offit
Tomas Kirchhoff
Mia M Gaudet
Joseph Vijai
Mark Robson
Marion Piedmonte
Kelly-Anne Phillips
Linda Van Le
James S Hoffman
Amanda Ewart Toland
Marco Montagna
Silvia Tognazzo
Evgeny Imyanitov
Claudine Issacs
Ramunas Janavicius
Conxi Lazaro
Iganacio Blanco
Eva Tornero
Matilde Navarro
Kirsten B Moysich
Beth Y Karlan
Jenny Gross
Edith Olah
Tibor Vaszko
Published in Human mutation
Volume 33
Issue 4
Pages 690-702
ISSN 1098-1004
Publication year 2012
Published at
Pages 690-702
Language en
Keywords Adult, BRCA1 Protein, genetics, BRCA2 Protein, genetics, Cohort Studies, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Middle Aged, Mutation, Odds Ratio, Ovarian Neoplasms, genetics, Polymorphism, Single Nucleotide, Retrospective Studies
Subject categories Cancer and Oncology, Medical Biotechnology

Abstract

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

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