TY - JOUR
T1 - 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
AU - EMBRACE
AU - Antoniou, Antonis C
AU - Wang, Xianshu
AU - Fredericksen, Zachary S
AU - McGuffog, Lesley
AU - Tarrell, Robert
AU - Sinilnikova, Olga M
AU - Healey, Sue
AU - Morrison, Jonathan
AU - Kartsonaki, Christiana
AU - Lesnick, Timothy
AU - Ghoussaini, Maya
AU - Barrowdale, Daniel
AU - Peock, Susan
AU - Cook, Margaret
AU - Oliver, Clare
AU - Frost, Debra
AU - Eccles, Diana
AU - Evans, D Gareth
AU - Eeles, Ros
AU - Izatt, Louise
AU - Chu, Carol
AU - Douglas, Fiona
AU - Paterson, Joan
AU - Stoppa-Lyonnet, Dominique
AU - Houdayer, Claude
AU - Mazoyer, Sylvie
AU - Giraud, Sophie
AU - Lasset, Christine
AU - Remenieras, Audrey
AU - Caron, Olivier
AU - Hardouin, Agnès
AU - Berthet, Pascaline
AU - Hogervorst, Frans B L
AU - Rookus, Matti A
AU - Jager, Agnes
AU - van den Ouweland, Ans
AU - Hoogerbrugge, Nicoline
AU - van der Luijt, Rob B
AU - Meijers-Heijboer, Hanne
AU - Gómez García, Encarna B
AU - Devilee, Peter
AU - Vreeswijk, Maaike P G
AU - Lubinski, Jan
AU - Jakubowska, Anna
AU - Gronwald, Jacek
AU - Huzarski, Tomasz
AU - Byrski, Tomasz
AU - Górski, Bohdan
AU - Cybulski, Cezary
AU - Hansen, Thomas V O
PY - 2010/10
Y1 - 2010/10
N2 - 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
AB - 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
KW - Adult
KW - BRCA1 Protein/genetics
KW - Breast Neoplasms/genetics
KW - Case-Control Studies
KW - Chromosomes, Human, Pair 19/genetics
KW - Female
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Mutation/genetics
KW - Polymorphism, Single Nucleotide/genetics
KW - Receptor, ErbB-2/genetics
KW - Receptors, Estrogen/genetics
KW - Receptors, Progesterone/genetics
U2 - 10.1038/ng.669
DO - 10.1038/ng.669
M3 - Article
C2 - 20852631
SN - 1061-4036
VL - 42
SP - 885
EP - 892
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -