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

被引：258

作者：

Antoniou, Antonis C. ^{[1
]}

Wang, Xianshu ^{[2
]}

Fredericksen, Zachary S. ^{[3
]}

McGuffog, Lesley ^{[1
]}

Tarrell, Robert ^{[3
]}

Sinilnikova, Olga M. ^{[4
,5
]}

Healey, Sue ^{[6
]}

Morrison, Jonathan ^{[1
]}

Kartsonaki, Christiana ^{[1
]}

Lesnick, Timothy ^{[3
]}

Ghoussaini, Maya ^{[6
]}

Barrowdale, Daniel ^{[1
]}

Peock, Susan ^{[1
]}

Cook, Margaret ^{[1
]}

Oliver, Clare ^{[1
]}

Frost, Debra ^{[1
]}

Eccles, Diana ^{[7
]}

Evans, D. Gareth ^{[8
]}

Eeles, Ros ^{[9
]}

Izatt, Louise ^{[10
]}

Chu, Carol ^{[11
]}

Douglas, Fiona ^{[12
]}

Paterson, Joan

Stoppa-Lyonnet, Dominique ^{[13
]}

Houdayer, Claude ^{[13
]}

Mazoyer, Sylvie ^{[5
]}

Giraud, Sophie ^{[4
]}

Lasset, Christine ^{[14
,15
]}

Remenieras, Audrey ^{[16
]}

Caron, Olivier ^{[17
]}

Hardouin, Agnes ^{[18
]}

Berthet, Pascaline ^{[18
]}

Hogervorst, Frans B. L. ^{[20
]}

Rookus, Matti A. ^{[21
]}

Jager, Agnes ^{[22
]}

van den Ouweland, Ans ^{[23
]}

Hoogerbrugge, Nicoline

van der Luijt, Rob B. ^{[24
]}

Meijers-Heijboer, Hanne ^{[25
]}

Garcia, Encarna B. Gomez ^{[26
]}

Devilee, Peter ^{[27
,28
]}

Vreeswijk, Maaike P. G. ^{[29
]}

Lubinski, Jan ^{[30
]}

Jakubowska, Anna ^{[30
]}

Gronwald, Jacek ^{[30
]}

Huzarski, Tomasz ^{[30
]}

Byrski, Tomasz ^{[30
]}

Gorski, Bohdan ^{[30
]}

Cybulski, Cezary ^{[30
]}

Spurdle, Amanda B. ^{[6
]}

机构：

[1] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[2] Dept Lab Med & Pathol, Mayo Clin, Rochester, MN USA

[3] Dept Hlth Sci Res, Mayo Clin, Rochester, MN USA

[4] Univ Lyon Ctr Leon Berard, Ctr Hosp, Unit Mixte Genet Constitutionnelle Canc Frequents, Lyon, France

[5] Univ Lyon, Ctr Leon Berard, CNRS, Equipe Labellisee LIGUE 2008, Lyon, France

[6] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[7] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England

[8] Cent Manchester Univ Hosp, Manchester Acad Hlth Sci Ctr, NHSFT, Manchester, Lancs, England

[9] Inst Canc Res & Royal Marsden NHS Fdn, Oncogenet Team, Sutton, Surrey, England

[10] Guys & St Thomas NHS Fdn Trust, Clin Genet, London, England

[11] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England

[12] Newcastle Tyne Hosp NHS Trust, Ctr Life, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England

[13] Univ Paris 05, Inst Curie, INSERM U509, Serv Genet Oncolog, Paris, France

[14] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France

[15] Ctr Leon Berard, Unit Prevent & Epidemiol Genet, Lyon, France

[16] Inst Cancerol Gustave Roussy, Dept Genet, Villejuif, France

[17] Inst Cancerol Gustave Roussy, Dept Med, Consultat Genet, Villejuif, France

[18] Ctr Francois Baclesse, F-14021 Caen, France

[19] Federat Natl Ctr Lutte Contre Canc, Grp Genet & Canc, Canc Genet Network, GEMO Study, Paris, France

[20] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands

[21] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands

[22] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands

[23] Rotterdam Family Canc Clin, Erasmus Univ Med Ctr, Dept Clin Genet, Rotterdam, Netherlands

[24] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[25] Vrije Univ Amsterdam, Dept Clin Genet, Amsterdam, Netherlands

[26] Maastricht Univ, Med Ctr, Dept Clin Genet, Sch Oncol & Dev Biol, Maastricht, Netherlands

[27] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands

[28] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands

[29] Leiden Univ, Med Ctr, Dept Toxicogenet, Leiden, Netherlands

[30] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland

[31] Peter MacCallum Canc Inst, Kathleen Cuningham Fdn Consortium Res Familial Br, kConFab, Melbourne, Vic 3000, Australia

[32] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA

[33] Stanford Univ, Sch Med, Canc Prevent Inst Calif, Stanford, CA USA

[34] Univ Melbourne, Melbourne, Vic, Australia

[35] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA

[36] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

[37] Columbia Univ, New York, NY USA

[38] Univ Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany

[39] Univ Cologne, CIO, Cologne, Germany

[40] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[41] Tech Univ Munich, Dept Obstet & Gynaecol, Div Tumor Genet, Klinikum Rechts Isar, Munich, Germany

[42] Univ Munster, Inst Human Genet, Munster, Germany

[43] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany

[44] Univ Dusseldorf, Univ Hosp Dusseldorf, Div Mol Genet, Dept Obstet & Gynaecol, Dusseldorf, Germany

[45] Heidelberg Univ, Div Mol Diagnost, Inst Human Genet, Heidelberg, Germany

[46] Univ Penn, Philadelphia, PA 19104 USA

[47] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA

[48] Roswell Pk Canc Inst, Gynecol Oncol Grp Stat & Data Ctr, Buffalo, NY 14263 USA

[49] Northshore Univ Hlth Syst, Evanston NW Healthcare, Evanston, IL USA

[50] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 10期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; COMMON VARIANTS; CONFER SUSCEPTIBILITY; OVARIAN-CANCER; NONSENSE; ALLELES; COMPLEX; 2Q35;

D O I：

10.1038/ng.669

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-9) to Ptrend = 3.9 x 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 (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).

引用

页码：885 / +

页数：11

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