Large-scale genotyping identifies 41 new loci associated with breast cancer risk

被引：843

作者：

Michailidou, Kyriaki ^{[1
]}

Hall, Per

Gonzalez-Neira, Anna ^{[3
]}

Ghoussaini, Maya ^{[4
]}

Dennis, Joe ^{[1
]}

Milne, Roger L. ^{[5
]}

Schmidt, Marjanka K. ^{[6
,7
]}

Chang-Claude, Jenny ^{[8
]}

Bojesen, Stig E. ^{[9
]}

Bolla, Manjeet K. ^{[1
]}

Wang, Qin ^{[1
]}

Dicks, Ed ^{[4
]}

Lee, Andrew ^{[1
]}

Turnbull, Clare ^{[11
]}

Rahman, Nazneen ^{[11
]}

Fletcher, Olivia ^{[12
]}

Peto, Julian ^{[13
]}

Gibson, Lorna ^{[13
]}

Silva, Isabel dos Santos ^{[13
]}

Nevanlinna, Heli ^{[14
,15
]}

Muranen, Taru A. ^{[14
,15
]}

Aittomaki, Kristiina ^{[15
,16
]}

Blomqvist, Carl ^{[15
,17
]}

Czene, Kamila ^{[2
]}

Irwanto, Astrid ^{[18
]}

Liu, Jianjun ^{[18
]}

Waisfisz, Quinten ^{[19
]}

Meijers-Heijboer, Hanne ^{[19
]}

Adank, Muriel ^{[19
]}

van der Luijt, Rob B. ^{[20
]}

Hein, Rebecca ^{[8
,21
]}

Dahmen, Norbert ^{[22
]}

Beckman, Lars ^{[23
]}

Meindl, Alfons ^{[24
]}

Schmutzler, Rita K. ^{[25
,26
]}

Mueller-Myhsok, Bertram ^{[27
]}

Lichtner, Peter ^{[28
]}

Hopper, John L. ^{[29
]}

Southey, Melissa C. ^{[30
]}

Makalic, Enes ^{[29
]}

Schmidt, Daniel F. ^{[29
]}

Uitterlinden, Andre G. ^{[31
]}

Hofman, Albert ^{[2
,3
,32
]}

Hunter, David J. ^{[33
]}

Chanock, Stephen J. ^{[34
]}

Vincent, Daniel ^{[35
,36
]}

Bacot, Francois ^{[35
,36
]}

Tessier, Daniel C. ^{[35
,36
]}

Canisius, Sander ^{[37
]}

Wessels, Lodewyk F. A. ^{[37
]}

机构：

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

[2] Karolinska Inst, Stockholm, Sweden

[3] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Human Genotyping Unit, Ctr Nacl Genotipado CEGEN, Madrid, Spain

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

[5] CNIO, Human Canc Genet Programme, Genet & Mol Epidemiol Grp, Madrid, Spain

[6] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands

[7] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands

[8] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, Heidelberg, Germany

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

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

[11] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England

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

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

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

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

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

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

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

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

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

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

[22] Johannes Gutenberg Univ Mainz, Dept Psychiat, D-55122 Mainz, Germany

[23] Inst Qual & Efficiency Hlth Care IQWiG, Cologne, Germany

[24] Tech Univ Munich, Clin Gynaecol & Obstet, Div Gynaecol Tumor Genet, D-80290 Munich, Germany

[25] Univ Cologne, Ctr Familial Breast & Ovarian Canc, D-50931 Cologne, Germany

[26] Univ Cologne, Ctr Mol Med CMMC, D-50931 Cologne, Germany

[27] Univ Cologne, Max Planck Inst Psychiat, D-50931 Cologne, Germany

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

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

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

[31] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[32] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

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

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

[35] McGill Univ, Montreal, PQ, Canada

[36] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[37] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands

[38] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

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

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

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

[42] VIB, Vesalius Res Ctr, Louvain, Belgium

[43] Univ Louvain, Dept Oncol, Lab Translat Genet, Louvain, Belgium

[44] Univ Louvain, Dept Oncol, Univ Hosp Gasthuisberg, Louvain, Belgium

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

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

[47] Sanquin Res, Amsterdam, Netherlands

[48] INSERM Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France

[49] Univ Paris 11, Unite Mixte Rech Sci UMRS 1018, Villejuif, France

[50] Univ Paris 04, INSERM, UMRS 775, Paris, France

来源：

NATURE GENETICS | 2013年 / 45卷 / 04期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; CONFER SUSCEPTIBILITY; SIGNALING PATHWAY; GENE; EXPRESSION; PROSTATE; ALLELES; 1P11.2;

D O I：

10.1038/ng.2563

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. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for similar to 9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 x 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.

引用

页码：353 / 361

页数：9

共 61 条

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French, Juliet D.
Ghoussaini, Maya
Edwards, Stacey L.
Meyer, Kerstin B.
Michailidou, Kyriaki
Ahmed, Shahana
Khan, Sofia
Maranian, Mel J.
O'Reilly, Martin
Hillman, Kristine M.
Betts, Joshua A.
Carro, Thomas
Bailey, Peter J.
Dicks, Ed
Beesley, Jonathan
Tyrer, Jonathan
Maia, Ana-Teresa
Beck, Andrew
Knoblauch, Nicholas W.
Chen, Constance
Kraft, Peter
Barnes, Daniel
Gonzalez-Neira, Anna
Rosario Alonso, M.
Herrero, Daniel
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Luccarini, Craig
Baynes, Caroline
Conroy, Don
Dennis, Joe
Bolla, Manjeet K.
Wang, Qin
Hopper, John L.
Southey, Melissa C.
Schmidt, Marjanka K.
Broeks, Annegien
Verhoef, Senno
Cornelissen, Sten
Muir, Kenneth
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pomthep
Fasching, Peter A.
Loehberg, Christian R.
Ekici, Arif B.
Beckmann, Matthias W.
Peto, Julian
Silva, Isabel dos Santos
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 92 (04) : 489 - 503
[22] Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk
Gaudet, Mia M.
Kuchenbaecker, Karoline B.
Vijai, Joseph
Klein, Robert J.
Kirchhoff, Tomas
McGuffog, Lesley
Barrowdale, Daniel
Dunning, Alison M.
Lee, Andrew
Dennis, Joe
Healey, Sue
Dicks, Ed
Soucy, Penny
Sinilnikova, Olga M.
Pankratz, Vernon S.
Wang, Xianshu
Eldridge, Ronald C.
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Hogervorst, Frans B. L.
Peock, Susan
Stoppa-Lyonnet, Dominique
Peterlongo, Paolo
Schmutzler, Rita K.
Nathanson, Katherine L.
Piedmonte, Marion
Singer, Christian F.
Thomassen, Mads
Hansen, Thomas V. O.
Neuhausen, Susan L.
Blanco, Ignacio
Greene, Mark H.
Garber, Judith
Weitzel, Jeffrey N.
Andrulis, Irene L.
Goldgar, David E.
D'Andrea, Emma
Caldes, Trinidad
Nevanlinna, Heli
Osorio, Ana
van Rensburg, Elizabeth J.
Arason, Adalgeir
Rennert, Gad
van den Ouweland, Ans M. W.
van der Hout, Annemarie H.
Kets, Carolien M.
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Wijnen, Juul T.
Ausems, Margreet G. E. M.
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Fletcher, Olivia
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Turnbull, Clare
Schmidt, Marjanka K.
Dicks, Ed
Dennis, Joe
Wang, Qin
Humphreys, Manjeet K.
Luccarini, Craig
Baynes, Caroline
Conroy, Don
Maranian, Melanie
Ahmed, Shahana
Driver, Kristy
Johnson, Nichola
Orr, Nicholas
Silva, Isabel dos Santos
Waisfisz, Quinten
Meijers-Heijboer, Hanne
Uitterlinden, Andre G.
Rivadeneira, Fernando
Hall, Per
Czene, Kamila
Irwanto, Astrid
Liu, Jianjun
Nevanlinna, Heli
Aittomaki, Kristiina
Blomqvist, Carl
Meindl, Alfons
Schmutzler, Rita K.
Mueller-Myhsok, Bertram
Lichtner, Peter
Chang-Claude, Jenny
Hein, Rebecca
Nickels, Stefan
Flesch-Janys, Dieter
Tsimiklis, Helen
Makalic, Enes
Schmidt, Daniel
Bui, Minh
Hopper, John L.
Apicella, Carmel
Park, Daniel J.
Southey, Melissa
Hunter, David J.
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Chenevix-Trench, Georgia
Song, Honglin
Ramus, Susan J.
Notaridou, Maria
Lawrenson, Kate
Widschwendter, Martin
Vierkant, Robert A.
Larson, Melissa C.
Kjaer, Susanne K.
Birrer, Michael J.
Berchuck, Andrew
Schildkraut, Joellen
Tomlinson, Ian
Kiemeney, Lambertus A.
Cook, Linda S.
Gronwald, Jacek
Garcia-Closas, Montserrat
Gore, Martin E.
Campbell, Ian
Whittemore, Alice S.
Sutphen, Rebecca
Phelan, Catherine
Anton-Culver, Hoda
Pearce, Celeste Leigh
Lambrechts, Diether
Rossing, Mary Anne
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Moysich, Kirsten B.
Goodman, Marc T.
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Houlston, Richard
van Altena, Anne M.
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Helgadottir, A
Styrkarsdottir, U
Magnusson, KP
Walters, GB
Palsdottir, E
Jonsdottir, T
Gudmundsdottir, T
Gylfason, A
Saemundsdottir, J
Wilensky, RL
Reilly, MP
Rader, DJ
Bagger, Y
Christiansen, C
Gudnason, V
Sigurdsson, G
Thorsteinsdottir, U
Gulcher, JR
Kong, A
Stefansson, K
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← 1 2 3 4 5 6 7 →

共 61 条

[21] Functional Variants at the 11q13 Risk Locus for Breast Cancer Regulate Cyclin D1 Expression through Long-Range Enhancers
French, Juliet D.
Ghoussaini, Maya
Edwards, Stacey L.
Meyer, Kerstin B.
Michailidou, Kyriaki
Ahmed, Shahana
Khan, Sofia
Maranian, Mel J.
O'Reilly, Martin
Hillman, Kristine M.
Betts, Joshua A.
Carro, Thomas
Bailey, Peter J.
Dicks, Ed
Beesley, Jonathan
Tyrer, Jonathan
Maia, Ana-Teresa
Beck, Andrew
Knoblauch, Nicholas W.
Chen, Constance
Kraft, Peter
Barnes, Daniel
Gonzalez-Neira, Anna
Rosario Alonso, M.
Herrero, Daniel
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Luccarini, Craig
Baynes, Caroline
Conroy, Don
Dennis, Joe
Bolla, Manjeet K.
Wang, Qin
Hopper, John L.
Southey, Melissa C.
Schmidt, Marjanka K.
Broeks, Annegien
Verhoef, Senno
Cornelissen, Sten
Muir, Kenneth
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pomthep
Fasching, Peter A.
Loehberg, Christian R.
Ekici, Arif B.
Beckmann, Matthias W.
Peto, Julian
Silva, Isabel dos Santos
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 92 (04) : 489 - 503
[22] Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk
Gaudet, Mia M.
Kuchenbaecker, Karoline B.
Vijai, Joseph
Klein, Robert J.
Kirchhoff, Tomas
McGuffog, Lesley
Barrowdale, Daniel
Dunning, Alison M.
Lee, Andrew
Dennis, Joe
Healey, Sue
Dicks, Ed
Soucy, Penny
Sinilnikova, Olga M.
Pankratz, Vernon S.
Wang, Xianshu
Eldridge, Ronald C.
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francois
Hogervorst, Frans B. L.
Peock, Susan
Stoppa-Lyonnet, Dominique
Peterlongo, Paolo
Schmutzler, Rita K.
Nathanson, Katherine L.
Piedmonte, Marion
Singer, Christian F.
Thomassen, Mads
Hansen, Thomas V. O.
Neuhausen, Susan L.
Blanco, Ignacio
Greene, Mark H.
Garber, Judith
Weitzel, Jeffrey N.
Andrulis, Irene L.
Goldgar, David E.
D'Andrea, Emma
Caldes, Trinidad
Nevanlinna, Heli
Osorio, Ana
van Rensburg, Elizabeth J.
Arason, Adalgeir
Rennert, Gad
van den Ouweland, Ans M. W.
van der Hout, Annemarie H.
Kets, Carolien M.
Aalfs, Cora M.
Wijnen, Juul T.
Ausems, Margreet G. E. M.
[J]. PLOS GENETICS, 2013, 9 (03):
[23] Genome-wide association analysis identifies three new breast cancer susceptibility loci
Ghoussaini, Maya
Fletcher, Olivia
Michailidou, Kyriaki
Turnbull, Clare
Schmidt, Marjanka K.
Dicks, Ed
Dennis, Joe
Wang, Qin
Humphreys, Manjeet K.
Luccarini, Craig
Baynes, Caroline
Conroy, Don
Maranian, Melanie
Ahmed, Shahana
Driver, Kristy
Johnson, Nichola
Orr, Nicholas
Silva, Isabel dos Santos
Waisfisz, Quinten
Meijers-Heijboer, Hanne
Uitterlinden, Andre G.
Rivadeneira, Fernando
Hall, Per
Czene, Kamila
Irwanto, Astrid
Liu, Jianjun
Nevanlinna, Heli
Aittomaki, Kristiina
Blomqvist, Carl
Meindl, Alfons
Schmutzler, Rita K.
Mueller-Myhsok, Bertram
Lichtner, Peter
Chang-Claude, Jenny
Hein, Rebecca
Nickels, Stefan
Flesch-Janys, Dieter
Tsimiklis, Helen
Makalic, Enes
Schmidt, Daniel
Bui, Minh
Hopper, John L.
Apicella, Carmel
Park, Daniel J.
Southey, Melissa
Hunter, David J.
Chanock, Stephen J.
Broeks, Annegien
Verhoef, Senno
Hogervorst, Frans B. L.
[J]. NATURE GENETICS, 2012, 44 (03) : 312 - U120
[24] A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24
Goode, Llen L.
Chenevix-Trench, Georgia
Song, Honglin
Ramus, Susan J.
Notaridou, Maria
Lawrenson, Kate
Widschwendter, Martin
Vierkant, Robert A.
Larson, Melissa C.
Kjaer, Susanne K.
Birrer, Michael J.
Berchuck, Andrew
Schildkraut, Joellen
Tomlinson, Ian
Kiemeney, Lambertus A.
Cook, Linda S.
Gronwald, Jacek
Garcia-Closas, Montserrat
Gore, Martin E.
Campbell, Ian
Whittemore, Alice S.
Sutphen, Rebecca
Phelan, Catherine
Anton-Culver, Hoda
Pearce, Celeste Leigh
Lambrechts, Diether
Rossing, Mary Anne
Chang-Claude, Jenny
Moysich, Kirsten B.
Goodman, Marc T.
Doerk, Thilo
Nevanlinna, Heli
Ness, Roberta B.
Rafnar, Thorunn
Hogdall, Claus
Hogdall, Estrid
Fridley, Brooke L.
Cunningham, Julie M.
Sieh, Weiva
McGuire, Valerie
Godwin, Andrew K.
Cramer, Daniel W.
Hernandez, Dena
Levine, Douglas
Lu, Karen
Iversen, Edwin S.
Palmieri, Rachel T.
Houlston, Richard
van Altena, Anne M.
Aben, Katja K. H.
[J]. NATURE GENETICS, 2010, 42 (10) : 874 - +
[25] Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Grant, SFA
Thorleifsson, G
Reynisdottir, I
Benediktsson, R
Manolescu, A
Sainz, J
Helgason, A
Stefansson, H
Emilsson, V
Helgadottir, A
Styrkarsdottir, U
Magnusson, KP
Walters, GB
Palsdottir, E
Jonsdottir, T
Gudmundsdottir, T
Gylfason, A
Saemundsdottir, J
Wilensky, RL
Reilly, MP
Rader, DJ
Bagger, Y
Christiansen, C
Gudnason, V
Sigurdsson, G
Thorsteinsdottir, U
Gulcher, JR
Kong, A
Stefansson, K
[J]. NATURE GENETICS, 2006, 38 (03) : 320 - 323
[26] A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
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.
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