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

被引：215

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：

英国惠康基金; 英国医学研究理事会;

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

共 67 条

[21] Novel Breast Cancer Susceptibility Locus at 9q31.2: Results of a Genome-Wide Association Study [J].

Fletcher, Olivia ;

Johnson, Nichola ;

Orr, Nick ;

Hosking, Fay J. ;

Gibson, Lorna J. ;

Walker, Kate ;

Zelenika, Diana ;

Gut, Ivo ;

Heath, Simon ;

Palles, Claire ;

Coupland, Ben ;

Broderick, Peter ;

Schoemaker, Minouk ;

Jones, Michael ;

Williamson, Jill ;

Chilcott-Burns, Sarah ;

Tomczyk, Katarzyna ;

Simpson, Gemma ;

Jacobs, Kevin B. ;

Chanock, Stephen J. ;

Hunter, David J. ;

Tomlinson, Ian P. ;

Swerdlow, Anthony ;

Ashworth, Alan ;

Ross, Gillian ;

Silva, Isabel dos Santos ;

Lathrop, Mark ;

Houlston, Richard S. ;

Peto, Julian .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2011, 103 (05) :425-435

[22]

FONTANA JA, 1992, CANCER RES, V52, P3938

[23] Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics [J].

Garcia-Closas, Montserrat ;

Hall, Per ;

Nevanlinna, Heli ;

Pooley, Karen ;

Morrison, Jonathan ;

Richesson, Douglas A. ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Arias, Jose I. ;

Milne, Roger L. ;

Ribas, Gloria ;

Gonzalez-Neira, Anna ;

Benitez, Javier ;

Zamora, Pilar ;

Brauch, Hiltrud ;

Justenhoven, Christina ;

Hamann, Ute ;

Ko, Yon-Dschun ;

Bruening, Thomas ;

Haas, Susanne ;

Doerk, Thilo ;

Schuermann, Peter ;

Hillemanns, Peter ;

Bogdanova, Natalia ;

Bremer, Michael ;

Karstens, Johann Hinrich ;

Fagerholm, Rainer ;

Aaltonen, Kirsimari ;

Aittomaki, Kristiina ;

Von Smitten, Karl ;

Blomqvist, Carl ;

Mannermaa, Arto ;

Uusitupa, Matti ;

Eskelinen, Matti ;

Tengstrom, Maria ;

Kosma, Veli-Matti ;

Kataja, Vesa ;

Chenevix-Trench, Georgia ;

Spurdle, Amanda B. ;

Beesley, Jonathan ;

Chen, Xiaoqing ;

Devilee, Peter ;

Van Asperen, Christi J. ;

Jacobi, Catharina E. ;

Tollenaar, Rob A. E. M. ;

Huijts, Petra E. A. ;

Klijn, Jan G. M. ;

Chang-Claude, Jenny ;

Kropp, Silke .

PLOS GENETICS, 2008, 4 (04)

[24] Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction [J].

Gudbjartsson, Daniel F. ;

Bjornsdottir, Unnur S. ;

Halapi, Eva ;

Helgadottir, Anna ;

Sulem, Patrick ;

Jonsdottir, Gudrun M. ;

Thorleifsson, Gudmar ;

Helgadottir, Hafdis ;

Steinthorsdottir, Valgerdur ;

Stefansson, Hreinn ;

Williams, Carolyn ;

Hui, Jennie ;

Beilby, John ;

Warrington, Nicole M. ;

James, Alan ;

Palmer, Lyle J. ;

Koppelman, Gerard H. ;

Heinzmann, Andrea ;

Krueger, Marcus ;

Boezen, H. Marike ;

Wheatley, Amanda ;

Altmuller, Janine ;

Shin, Hyoung Doo ;

Uh, Soo-Taek ;

Cheong, Hyun Sub ;

Jonsdottir, Brynja ;

Gislason, David ;

Park, Choon-Sik ;

Rasmussen, Linda M. ;

Porsbjerg, Celeste ;

Hansen, Jakob W. ;

Backer, Vibeke ;

Werge, Thomas ;

Janson, Christer ;

Joensson, Ulla-Britt ;

Ng, Maggie C. Y. ;

Chan, Juliana ;

So, Wing Yee ;

Ma, Ronald ;

Shah, Svati H. ;

Granger, Christopher B. ;

Quyyumi, Arshed A. ;

Levey, Allan I. ;

Vaccarino, Viola ;

Reilly, Muredach P. ;

Rader, Daniel J. ;

Williams, Michael J. A. ;

van Rij, Andre M. ;

Jones, Gregory T. ;

Trabetti, Elisabetta .

NATURE GENETICS, 2009, 41 (03) :342-347

[25] A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer [J].

Haiman, Christopher A. ;

Chen, Gary K. ;

Vachon, Celine M. ;

Canzian, Federico ;

Dunning, Alison ;

Millikan, Robert C. ;

Wang, Xianshu ;

Ademuyiwa, Foluso ;

Ahmed, Shahana ;

Ambrosone, Christine B. ;

Baglietto, Laura ;

Balleine, Rosemary ;

Bandera, Elisa V. ;

Beckmann, Matthias W. ;

Berg, Christine D. ;

Bernstein, Leslie ;

Blomqvist, Carl ;

Blot, William J. ;

Brauch, Hiltrud ;

Buring, Julie E. ;

Carey, Lisa A. ;

Carpenter, Jane E. ;

Chang-Claude, Jenny ;

Chanock, Stephen J. ;

Chasman, Daniel I. ;

Clarke, Christine L. ;

Cox, Angela ;

Cross, Simon S. ;

Deming, Sandra L. ;

Diasio, Robert B. ;

Dimopoulos, Athanasios M. ;

Driver, W. Ryan ;

Duennebier, Thomas ;

Durcan, Lorraine ;

Eccles, Diana ;

Edlund, Christopher K. ;

Ekici, Arif B. ;

Fasching, Peter A. ;

Feigelson, Heather S. ;

Flesch-Janys, Dieter ;

Fostira, Florentia ;

Foersti, Asta ;

Fountzilas, George ;

Gerty, Susan M. ;

Giles, Graham G. ;

Godwin, Andrew K. ;

Goodfellow, Paul ;

Graham, Nikki ;

Greco, Dario ;

Hamann, Ute .

NATURE GENETICS, 2011, 43 (12) :1210-U61

[26]

HENDERSON JE, 1995, MOL CELL BIOL, V15, P4064

[27] Parathyroid hormone-related protein localization in breast cancers predict improved prognosis [J].

Henderson, MA ;

Danks, JA ;

Slavin, JL ;

Byrnes, GB ;

Choong, PFM ;

Spillane, JB ;

Hopper, JL ;

Martin, TJ .

CANCER RESEARCH, 2006, 66 (04) :2250-2256

[28] A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer [J].

Hunter, David J. ;

Kraft, Peter ;

Jacobs, Kevin B. ;

Cox, David G. ;

Yeager, Meredith ;

Hankinson, Susan E. ;

Wacholder, Sholom ;

Wang, Zhaoming ;

Welch, Robert ;

Hutchinson, Amy ;

Wang, Junwen ;

Yu, Kai ;

Chatterjee, Nilanjan ;

Orr, Nick ;

Willett, Walter C. ;

Colditz, Graham A. ;

Ziegler, Regina G. ;

Berg, Christine D. ;

Buys, Saundra S. ;

McCarty, Catherine A. ;

Feigelson, Heather Spencer ;

Calle, Eugenia E. ;

Thun, Michael J. ;

Hayes, Richard B. ;

Tucker, Margaret ;

Gerhard, Daniela S. ;

Fraumeni, Joseph F., Jr. ;

Hoover, Robert N. ;

Thomas, Gilles ;

Chanock, Stephen J. .

NATURE GENETICS, 2007, 39 (07) :870-874

[29] SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap [J].

Johnson, Andrew D. ;

Handsaker, Robert E. ;

Pulit, Sara L. ;

Nizzari, Marcia M. ;

O'Donnell, Christopher J. ;

de Bakker, Paul I. W. .

BIOINFORMATICS, 2008, 24 (24) :2938-2939

[30] A G-PROTEIN LINKED RECEPTOR FOR PARATHYROID-HORMONE AND PARATHYROID-HORMONE RELATED PEPTIDE [J].

JUPPNER, H ;

ABOUSAMRA, AB ;

FREEMAN, M ;

KONG, XF ;

SCHIPANI, E ;

RICHARDS, J ;

KOLAKOWSKI, LF ;

HOCK, J ;

POTTS, JT ;

KRONENBERG, HM ;

SEGRE, GV .

SCIENCE, 1991, 254 (5034) :1024-1026

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