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

Antonis C Antoniou, Xianshu Wang, Zachary S Fredericksen, Lesley McGuffog, Robert Tarrell, Olga M Sinilnikova, Sue Healey, Jonathan Morrison, Christiana Kartsonaki, Timothy Lesnick, Maya Ghoussaini, Daniel Barrowdale, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Diana Eccles, D Gareth Evans, Ros Eeles, Louise Izatt & 31 andre Carol Chu, Fiona Douglas, Joan Paterson, Dominique Stoppa-Lyonnet, Claude Houdayer, Sylvie Mazoyer, Sophie Giraud, Christine Lasset, Audrey Remenieras, Olivier Caron, Agnès Hardouin, Pascaline Berthet, Frans B L Hogervorst, Matti A Rookus, Agnes Jager, Ans van den Ouweland, Nicoline Hoogerbrugge, Rob B van der Luijt, Hanne Meijers-Heijboer, Encarna B Gómez García, Peter Devilee, Maaike P G Vreeswijk, Jan Lubinski, Anna Jakubowska, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Bohdan Górski, Anne-Marie Gerdes, Mads Thomassen, EMBRACE

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind42
Udgave nummer10
Sider (fra-til)885-92
Antal sider8
ISSN1061-4036
DOI
StatusUdgivet - 1. okt. 2010

Fingeraftryk

Hormones
Mutation
Single Nucleotide Polymorphism
Population
Odds Ratio
Alleles
Germ-Line Mutation
Genome-Wide Association Study

Citer dette

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 ; Gerdes, Anne-Marie ; Thomassen, Mads ; EMBRACE. / 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. I: Nature Genetics. 2010 ; Bind 42, Nr. 10. s. 885-92.
@article{571a1c98a4214dff960862214f756c04,
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",
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",
keywords = "Adult, BRCA1 Protein, Breast Neoplasms, Case-Control Studies, Chromosomes, Human, Pair 19, Female, Genetic Predisposition to Disease, Genotype, Humans, Mutation, Polymorphism, Single Nucleotide, Receptor, erbB-2, Receptors, Estrogen, Receptors, Progesterone",
author = "Antoniou, {Antonis C} and Xianshu Wang and Fredericksen, {Zachary S} and Lesley McGuffog and Robert Tarrell and Sinilnikova, {Olga M} and Sue Healey and Jonathan Morrison and Christiana Kartsonaki and Timothy Lesnick and Maya Ghoussaini and Daniel Barrowdale and Susan Peock and Margaret Cook and Clare Oliver and Debra Frost and Diana Eccles and Evans, {D Gareth} and Ros Eeles and Louise Izatt and Carol Chu and Fiona Douglas and Joan Paterson and Dominique Stoppa-Lyonnet and Claude Houdayer and Sylvie Mazoyer and Sophie Giraud and Christine Lasset and Audrey Remenieras and Olivier Caron and Agn{\`e}s Hardouin and Pascaline Berthet and Hogervorst, {Frans B L} and Rookus, {Matti A} and Agnes Jager and {van den Ouweland}, Ans and Nicoline Hoogerbrugge and {van der Luijt}, {Rob B} and Hanne Meijers-Heijboer and {G{\'o}mez Garc{\'i}a}, {Encarna B} and Peter Devilee and Vreeswijk, {Maaike P G} and Jan Lubinski and Anna Jakubowska and Jacek Gronwald and Tomasz Huzarski and Tomasz Byrski and Bohdan G{\'o}rski and Anne-Marie Gerdes and Mads Thomassen and EMBRACE",
year = "2010",
month = "10",
day = "1",
doi = "10.1038/ng.669",
language = "English",
volume = "42",
pages = "885--92",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "10",

}

Antoniou, AC, Wang, X, Fredericksen, ZS, McGuffog, L, Tarrell, R, Sinilnikova, OM, Healey, S, Morrison, J, Kartsonaki, C, Lesnick, T, Ghoussaini, M, Barrowdale, D, Peock, S, Cook, M, Oliver, C, Frost, D, Eccles, D, Evans, DG, Eeles, R, Izatt, L, Chu, C, Douglas, F, Paterson, J, Stoppa-Lyonnet, D, Houdayer, C, Mazoyer, S, Giraud, S, Lasset, C, Remenieras, A, Caron, O, Hardouin, A, Berthet, P, Hogervorst, FBL, Rookus, MA, Jager, A, van den Ouweland, A, Hoogerbrugge, N, van der Luijt, RB, Meijers-Heijboer, H, Gómez García, EB, Devilee, P, Vreeswijk, MPG, Lubinski, J, Jakubowska, A, Gronwald, J, Huzarski, T, Byrski, T, Górski, B, Gerdes, A-M, Thomassen, M & EMBRACE 2010, '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, bind 42, nr. 10, s. 885-92. https://doi.org/10.1038/ng.669

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. / 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; Gerdes, Anne-Marie; Thomassen, Mads; EMBRACE.

I: Nature Genetics, Bind 42, Nr. 10, 01.10.2010, s. 885-92.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - 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 - Gerdes, Anne-Marie

AU - Thomassen, Mads

AU - EMBRACE

PY - 2010/10/1

Y1 - 2010/10/1

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

KW - Breast Neoplasms

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 19

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Mutation

KW - Polymorphism, Single Nucleotide

KW - Receptor, erbB-2

KW - Receptors, Estrogen

KW - Receptors, Progesterone

U2 - 10.1038/ng.669

DO - 10.1038/ng.669

M3 - Journal article

VL - 42

SP - 885

EP - 892

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -