Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
Creators: name: Antoniou, Antonis
name: Kuchenbaecker, Karoline
name: Soucy, Penny
name: Beesley, Jonathan
name: Chen, Xiaoqing
name: McGuffog, Lesley
name: Lee, Andrew
name: Barrowdale, Daniel
name: Healey, Sue
name: Sinilnikova, Olga
name: Caligo, Maria
name: Loman, Niklas
name: Harbst, Katja
name: Lindblom, Annika
name: Arver, Brita
name: Rosenquist, Richard
name: Karlsson, Per
name: Nathanson, Kate
name: Domchek, Susan
name: Rebbeck, Tim
name: Jakubowska, Anna
name: Lubinski, Jan
name: Jaworska, Katarzyna
name: Durda, Katarzyna
name: Złowowcka-Perłowska, Elżbieta
name: Osorio, Ana
name: Durán, Mercedes
name: Andrés, Raquel
name: Benítez, Javier
name: Hamann, Ute
name: Hogervorst, Frans
name: Van Os, Theo
name: Verhoef, Senno
name: Meijers-Heijboer, Hanne
name: Wijnen, Juul
name: Gómez Garcia, Encarna
name: Ligtenberg, Marjolijn
name: Kriege, Mieke
name: Collée, J. Margriet
name: Ausems, Margreet
name: Oosterwijk, Jan
name: Peock, Susan
name: Frost, Debra
name: Ellis, Steve
name: Platte, Radka
name: Fineberg, Elena
name: Evans, D. Gareth
name: Lalloo, Fiona
name: Jacobs, Chris
name: Eeles, Ros
name: Adlard, Julian
name: Davidson, Rosemarie
name: Cole, Trevor
name: Cook, Jackie
name: Paterson, Joan
name: Douglas, Fiona
name: Brewer, Carole
name: Hodgson, Shirley
name: Morrison, Patrick
name: Walker, Lisa
name: Rogers, Mark
name: Donaldson, Alan
name: Dorkins, Huw
name: Godwin, Andrew
name: Bove, Betsy
name: Stoppa-Lyonnet, Dominique
name: Houdayer, Claude
name: Buecher, Bruno
name: De Pauw, Antoine
name: Mazoyer, Sylvie
name: Calender, Alain
name: Léoné, Mélanie
name: Bressac-De Paillerets, Brigitte
name: Caron, Olivier
name: Sobol, Hagay
name: Frenay, Marc
name: Prieur, Fabienne
name: Ferrer, Sandra
name: Mortemousque, Isabelle
name: Buys, Saundra
name: Daly, Mary
name: Miron, Alexander
name: Terry, Mary Beth
name: Hopper, John
name: John, Esther
name: Southey, Melissa
name: Goldgar, David
name: Singer, Christian
name: Fink-Retter, Anneliese
name: Tea, Muy-Kheng
name: Kaulich, Daphne
name: Hansen, Thomas
name: Nielsen, Finn
name: Barkardottir, Rosa
name: Gaudet, Mia
name: Kirchhoff, Tomas
name: Joseph, Vijai
name: Dutra-Clarke, Ana
name: Offit, Kenneth
name: Piedmonte, Marion
name: Kirk, Judy
name: Cohn, David
name: Hurteau, Jean
name: Byron, John
name: Fiorica, James
name: Toland, Amanda
name: Montagna, Marco
name: Oliani, Cristina
name: Imyanitov, Evgeny
name: Isaacs, Claudine
name: Tihomirova, Laima
name: Blanco, Ignacio
name: Lazaro, Conxi
name: Teulé, Alex
name: Valle, J. Del
name: Gayther, Simon
name: Odunsi, Kunle
name: Gross, Jenny
name: Karlan, Beth
name: Olah, Edith
name: Teo, Soo-Hwang
name: Ganz, Patricia
name: Beattie, Mary
name: Dorfling, Cecelia
name: Van Rensburg, Elizabeth
name: Diez, Orland
name: Kwong, Ava
name: Schmutzler, Rita
name: Wappenschmidt, Barbara
name: Engel, Christoph
name: Meindl, Alfons
name: Ditsch, Nina
name: Arnold, Norbert
name: Heidemann, Simone
name: Niederacher, Dieter
name: Preisler-Adams, Sabine
name: Gadzicki, Dorothea
name: Varon-Mateeva, Raymonda
name: Deissler, Helmut
name: Gehrig, Andrea
name: Sutter, Christian
name: Kast, Karin
name: Fiebig, Britta
name: Schäfer, Dieter
name: Caldes, Trinidad
name: De La Hoya, Miguel
name: Nevanlinna, Heli
name: Muranen, Taru
name: Lespérance, Bernard
name: Spurdle, Amanda
name: Neuhausen, Susan
name: Ding, Yuan
name: Wang, Xianshu
name: Fredericksen, Zachary
name: Pankratz, Vernon
name: Lindor, Noralane
name: Peterlongo, Paolo
name: Manoukian, Siranoush
name: Peissel, Bernard
name: Zaffaroni, Daniela
name: Bonanni, Bernardo
name: Bernard, Loris
name: Dolcetti, Riccardo
name: Papi, Laura
name: Ottini, Laura
name: Radice, Paolo
name: Greene, Mark
name: Loud, Jennifer
name: Andrulis, Irene
name: Ozcelik, Hilmi
name: Mulligan, Anna
name: Glendon, Gord
name: Thomassen, Mads
name: Gerdes, Anne-Marie
name: Jensen, Uffe
name: Skytte, Anne-Bine
name: Kruse, Torben
name: Chenevix-Trench, Georgia
name: Couch, Fergus
name: Simard, Jacques
name: Easton, Douglas
Publisher: name: Columbia University
Year: 2012
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.