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PMID: 20852631 Published · ppublish English

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.

Nature genetics ·Vol. 42 ·No. 10 ·2010-10-28

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, Barrowdale Daniel, , Peock Susan, Cook Margaret, Oliver Clare, Frost Debra, Eccles Diana, Evans D Gareth, 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, 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, Nielsen Finn C, Blanco Ignacio, Lazaro Conxi, Garber Judy, Ramus Susan J, Gayther Simon A, Phelan Catherine, Narod Stephen, Szabo Csilla I, , Benitez Javier, Osorio Ana, Nevanlinna Heli, Heikkinen Tuomas, Caligo Maria A, Beattie Mary S, Hamann Ute, Godwin Andrew K, Montagna Marco, Casella Cinzia, Neuhausen Susan L, Karlan Beth Y, Tung Nadine, Toland Amanda E, Weitzel Jeffrey, Olopade Olofunmilayo, Simard Jacques, Soucy Penny, Rubinstein Wendy S, Arason Adalgeir, Rennert Gad, 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, 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, Rüdiger Thomas, Försti Asta, Winqvist Robert, Pylkäs Katri, Diasio Robert B, Lee Adam M, Eckel-Passow Jeanette, Vachon Celine, Blows Fiona, Driver Kristy, Dunning Alison, Pharoah Paul P D, Offit Kenneth, Pankratz V Shane, Hakonarson Hakon, Chenevix-Trench Georgia, Easton Douglas F, Couch Fergus J

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

Article Info
Journal
Nature genetics
Abbr.
Nat Genet
Published
2010-10-28
Indexed
2010-09-29
Updated
2016-11-22
Language
English
Country/Region
United States
NLM ID
9216904
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