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Title: A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
Authors: Antoniou, Antonis C
Wang, Xianshu
Fredericksen, Zachary S
McGuffog, Lesley
Tarrell, Robert
Sinilnikova, Olga M
Healey, Sue
Morrison, Jonathan
Kartsonaki, Christiana
Lesnick, Timothy
Ghoussaini, Maya
Caldes, Trinidad
de la Hoya, Miguel
Singer, Christian F
Fink-Retter, Anneliese
Greene, Mark H
Mai, Phuong L
Loud, Jennifer T
Guidugli, Lucia
Lindor, Noralane M
Hansen, Thomas V O
Barrowdale, Daniel
Nielsen, Finn C
Blanco, Ignacio
Lazaro, Conxi
Garber, Judy
Ramus, Susan J
Gayther, Simon A
Phelan, Catherine
Narod, Stephen
Szabo, Csilla I
Benitez, Javier
Peock, Susan
Osorio, Ana
Nevanlinna, Heli
Heikkinen, Tuomas
Caligo, Maria A
Beattie, Mary S
Hamann, Ute
Godwin, Andrew K
Montagna, Marco
Casella, Cinzia
Neuhausen, Susan L
Cook, Margaret
Karlan, Beth Y
Tung, Nadine
Toland, Amanda E
Weitzel, Jeffrey
Olopade, Olofunmilayo
Simard, Jacques
Soucy, Penny
Rubinstein, Wendy S
Arason, Adalgeir
Rennert, Gad
Oliver, Clare
Martin, Nicholas G
Montgomery, Grant W
Chang-Claude, Jenny
Flesch-Janys, Dieter
Brauch, Hiltrud
Severi, Gianluca
Baglietto, Laura
Cox, Angela
Cross, Simon S
Miron, Penelope
Frost, Debra
Gerty, Sue M
Tapper, William
Yannoukakos, Drakoulis
Fountzilas, George
Fasching, Peter A
Beckmann, Matthias W
Dos Santos Silva, Isabel
Peto, Julian
Lambrechts, Diether
Paridaens, Robert
Eccles, Diana
Rüdiger, Thomas
Försti, Asta
Winqvist, Robert
Pylkäs, Katri
Diasio, Robert B
Lee, Adam M
Eckel-Passow, Jeanette
Vachon, Celine
Blows, Fiona
Driver, Kristy
Evans, D Gareth
Dunning, Alison
Pharoah, Paul P D
Offit, Kenneth
Pankratz, V Shane
Hakonarson, Hakon
Chenevix-Trench, Georgia
Easton, Douglas F
Couch, Fergus J ×
Eeles, Ros
Izatt, Louise
Chu, Carol
Douglas, Fiona
Paterson, Joan
Stoppa-Lyonnet, Dominique
Houdayer, Claude
Mazoyer, Sylvie
Giraud, Sophie
Lasset, Christine
Remenieras, Audrey
Caron, Olivier
Hardouin, Agnès
Berthet, Pascaline
Hogervorst, Frans B L
Rookus, Matti A
Jager, Agnes
van den Ouweland, Ans
Hoogerbrugge, Nicoline
van der Luijt, Rob B
Meijers-Heijboer, Hanne
Gómez García, Encarna B
Devilee, Peter
Vreeswijk, Maaike P G
Lubinski, Jan
Jakubowska, Anna
Gronwald, Jacek
Huzarski, Tomasz
Byrski, Tomasz
Górski, Bohdan
Cybulski, Cezary
Spurdle, Amanda B
Holland, Helene
Goldgar, David E
John, Esther M
Hopper, John L
Southey, Melissa
Buys, Saundra S
Daly, Mary B
Terry, Mary-Beth
Schmutzler, Rita K
Wappenschmidt, Barbara
Engel, Christoph
Meindl, Alfons
Preisler-Adams, Sabine
Arnold, Norbert
Niederacher, Dieter
Sutter, Christian
Domchek, Susan M
Nathanson, Katherine L
Rebbeck, Timothy
Blum, Joanne L
Piedmonte, Marion
Rodriguez, Gustavo C
Wakeley, Katie
Boggess, John F
Basil, Jack
Blank, Stephanie V
Friedman, Eitan
Kaufman, Bella
Laitman, Yael
Milgrom, Roni
Andrulis, Irene L
Glendon, Gord
Ozcelik, Hilmi
Kirchhoff, Tomas
Vijai, Joseph
Gaudet, Mia M
Altshuler, David
Guiducci, Candace
Loman, Niklas
Harbst, Katja
Rantala, Johanna
Ehrencrona, Hans
Gerdes, Anne-Marie
Thomassen, Mads
Sunde, Lone
Peterlongo, Paolo
Manoukian, Siranoush
Bonanni, Bernardo
Viel, Alessandra
Radice, Paolo #
Issue Date: Oct-2010
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:42 issue:10 pages:885-892
Abstract: Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P(trend) = 2.3 × 10⁻⁹ to P(trend) = 3.9 × 10⁻⁷), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (P(trend) = 1 × 10⁻⁷) to P(trend) = 8 × 10⁻⁵; rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P(trend) = 1.1 × 10⁻⁷
URI: 
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Experimental Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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