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Title: Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk
Author: Couch, Fergus J.
Wang, Xianshu
McGuffog, Lesley
Lee, Andrew
Olswold, Curtis
Kuchenbaecker, Karoline B.
Soucy, Penny
Fredericksen, Zachary
Barrowdale, Daniel
Dennis, Joe
Gaudet, Mia M.
Dicks, Ed
Kosel, Matthew
Healey, Sue
Sinilnikova, Olga M.
Bacot, François
Vincent, Daniel
Hogervorst, Frans B. L.
Peock, Susan
Stoppa-Lyonnet, Dominique
Jakubowska, Anna
Radice, Paolo
Schmutzler, Rita Katharina
Domchek, Susan M.
Piedmonte, Marion
Singer, Christian F.
Friedman, Eitan
Thomassen, Mads
Hansen, Thomas V. O.
Neuhausen, Susan L.
Szabo, Csilla I.
Blanco Guillermo, Ignacio
Greene, Mark H.
Karlan, Beth Y.
Garber, Judy
Phelan, Catherine M.
Weitzel, Jeffrey N.
Montagna, Marco
Olah, Edith
Keywords: Càncer de mama
Càncer d'ovari
Malalties hereditàries
Genètica humana
Breast cancer
Ovarian cancer
Genetic diseases
Human genetics
Issue Date: 27-Mar-2013
Publisher: Public Library of Science (PLoS)
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10−8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10−8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10−8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10−4). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
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It is part of: PLoS Genetics, 2013, vol. 9, num. 3, p. e1003212
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ISSN: 1553-7390
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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