TY - JOUR
T1 - Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
AU - Antoniou, Antonis C
AU - Kartsonaki, Christiana
AU - Sinilnikova, Olga M
AU - Soucy, Penny
AU - McGuffog, Lesley
AU - Healey, Sue
AU - Lee, Andrew
AU - Peterlongo, Paolo
AU - Manoukian, Siranoush
AU - Peissel, Bernard
AU - Zaffaroni, Daniela
AU - Cattaneo, Elisa
AU - Barile, Monica
AU - Pensotti, Valeria
AU - Pasini, Barbara
AU - Dolcetti, Riccardo
AU - Giannini, Giuseppe
AU - Putignano, Anna Laura
AU - Varesco, Liliana
AU - Radice, Paolo
AU - Mai, Phuong L
AU - Greene, Mark H
AU - Andrulis, Irene L
AU - Glendon, Gord
AU - Ozcelik, Hilmi
AU - Thomassen, Mads
AU - Gerdes, Anne-Marie
AU - Kruse, Torben A
AU - Birk Jensen, Uffe
AU - Crüger, Dorthe G
AU - Caligo, Maria A
AU - Laitman, Yael
AU - Milgrom, Roni
AU - Kaufman, Bella
AU - Paluch-Shimon, Shani
AU - Friedman, Eitan
AU - Loman, Niklas
AU - Harbst, Katja
AU - Lindblom, Annika
AU - Arver, Brita
AU - Ehrencrona, Hans
AU - Melin, Beatrice
AU - Nathanson, Katherine L
AU - Domchek, Susan M
AU - Rebbeck, Timothy
AU - Jakubowska, Ania
AU - Lubinski, Jan
AU - Gronwald, Jacek
AU - Huzarski, Tomasz
AU - Miedzybrodzka, Zosia
AU - SWE-BRCA
PY - 2011/8/15
Y1 - 2011/8/15
N2 - Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
AB - Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
KW - adult
KW - aged
KW - alleles
KW - BRCA1 protein
KW - BRCA2 protein
KW - breast neoplasms
KW - chromosomes, human
KW - chromosomes, human, pair 1
KW - chromosomes, human, pair 6
KW - female
KW - genetic predisposition to disease
KW - heterozygote
KW - humans
KW - middle aged
KW - mutation
KW - polymorphism, single nucleotide
KW - risk factors
U2 - 10.1093/hmg/ddr226
DO - 10.1093/hmg/ddr226
M3 - Article
C2 - 21593217
VL - 20
SP - 3304
EP - 3321
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 16
ER -