Genome-wide association analysis identifies three new breast cancer susceptibility loci

被引：213

作者：

Ghoussaini, Maya ^{[1
]}

Fletcher, Olivia ^{[2
]}

Michailidou, Kyriaki ^{[3
]}

Turnbull, Clare ^{[4
]}

Schmidt, Marjanka K. ^{[5
,6
]}

Dicks, Ed ^{[1
]}

Dennis, Joe ^{[3
]}

Wang, Qin ^{[3
]}

Humphreys, Manjeet K. ^{[3
]}

Luccarini, Craig ^{[1
]}

Baynes, Caroline ^{[1
]}

Conroy, Don ^{[1
]}

Maranian, Melanie ^{[1
]}

Ahmed, Shahana ^{[1
]}

Driver, Kristy ^{[1
]}

Johnson, Nichola ^{[2
]}

Orr, Nicholas ^{[2
]}

Silva, Isabel dos Santos ^{[7
]}

Waisfisz, Quinten ^{[8
]}

Meijers-Heijboer, Hanne ^{[8
]}

Uitterlinden, Andre G. ^{[9
]}

Rivadeneira, Fernando ^{[9
]}

Hall, Per ^{[10
]}

Czene, Kamila ^{[10
]}

Irwanto, Astrid ^{[11
,12
]}

Liu, Jianjun ^{[13
]}

Nevanlinna, Heli ^{[11
,12
]}

Aittomaki, Kristiina ^{[12
,14
]}

Blomqvist, Carl ^{[12
,15
]}

Meindl, Alfons ^{[16
]}

Schmutzler, Rita K. ^{[17
]}

Mueller-Myhsok, Bertram ^{[18
]}

Lichtner, Peter ^{[19
]}

Chang-Claude, Jenny ^{[20
]}

Hein, Rebecca ^{[20
,21
]}

Nickels, Stefan ^{[20
]}

Flesch-Janys, Dieter ^{[22
,23
]}

Tsimiklis, Helen ^{[24
]}

Makalic, Enes ^{[25
]}

Schmidt, Daniel ^{[25
]}

Bui, Minh ^{[25
]}

Hopper, John L. ^{[25
]}

Apicella, Carmel ^{[25
]}

Park, Daniel J. ^{[24
]}

Southey, Melissa ^{[24
]}

Hunter, David J. ^{[26
]}

Chanock, Stephen J. ^{[27
]}

Broeks, Annegien ^{[5
]}

Verhoef, Senno ^{[28
]}

Hogervorst, Frans B. L. ^{[29
]}

机构：

[1] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[2] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

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

[4] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[5] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands

[6] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands

[7] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England

[8] Vrije Univ Amsterdam Med Ctr, Sect Oncogenet, Dept Clin Genet, Amsterdam, Netherlands

[9] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands

[10] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[11] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland

[12] Univ Helsinki, Cent Hosp, Helsinki, Finland

[13] Genome Inst Singapore, Human Genet Div, Singapore, Singapore

[14] Univ Helsinki, Dept Clin Genet, Helsinki, Finland

[15] Univ Helsinki, Dept Oncol, Helsinki, Finland

[16] Tech Univ Munich, Div Gynaecol Tumor Genet, Clin Gynaecol & Obstet, Munich, Germany

[17] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaecooncol, D-50931 Cologne, Germany

[18] Max Planck Inst Psychiat, D-80804 Munich, Germany

[19] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[20] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, D-6900 Heidelberg, Germany

[21] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, Primar Med Versorgung PMV Res Grp, D-50931 Cologne, Germany

[22] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany

[23] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany

[24] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia

[25] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[26] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

[27] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[28] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Clin Genet, Amsterdam, Netherlands

[29] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Mol Pathol, Amsterdam, Netherlands

[30] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, Erlangen, Germany

[31] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany

[32] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Div Canc Studies, Natl Inst Hlth Res NIHR Comprehens Biomed Res Ctr, London, England

[33] Kings Coll London, Div Canc Studies, London WC2R 2LS, England

[34] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England

[35] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[36] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland

[37] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[38] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany

[39] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany

[40] Ctr Rech Epidemiol & Populat Hlth CESP, INSERM, U1018, Villejuif, France

[41] Univ Paris 11, Unite Mixte Rech Sante UMRS 1018, Villejuif, France

[42] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark

[43] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark

[44] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark

[45] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Genet & Mol Epidemiol Grp, Madrid, Spain

[46] CNIO, Human Canc Genet Programme, Human Genotyping Unit, Madrid, Spain

[47] CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain

[48] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA

[49] City Hope Canc Ctr, Duarte, CA USA

[50] Canc Prevent Inst Calif, Fremont, CA USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

HORMONE-RELATED PROTEIN; PARATHYROID-HORMONE; NEGATIVE-FEEDBACK; COMMON VARIANTS; CONFER SUSCEPTIBILITY; GENE-EXPRESSION; CELL CARCINOMA; RETINOIC ACID; MAMMARY-GLAND; RECEPTOR;

D O I：

10.1038/ng.1049

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

引用

页码：312 / U120

页数：8

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