Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

被引：378

作者：

Ahmed, Shahana ^{[2
]}

Thomas, Gilles ^{[3
]}

Ghoussaini, Maya ^{[2
]}

Healey, Catherine S. ^{[2
]}

Humphreys, Manjeet K. ^{[1
]}

Platte, Radka ^{[2
]}

Morrison, Jonathan ^{[1
]}

Maranian, Melanie ^{[2
]}

Pooley, Karen A. ^{[1
]}

Luben, Robert ^{[4
]}

Eccles, Diana ^{[5
]}

Evans, D. Gareth ^{[6
]}

Fletcher, Olivia ^{[7
,8
]}

Johnson, Nichola ^{[7
]}

Silva, Isabel dos Santos ^{[8
]}

Peto, Julian ^{[8
]}

Stratton, Michael R. ^{[9
]}

Rahman, Nazneen ^{[87
]}

Jacobs, Kevin ^{[3
,10
,11
]}

Prentice, Ross ^{[12
]}

Anderson, Garnet L. ^{[12
]}

Rajkovic, Aleksandar ^{[13
]}

Curb, J. David ^{[14
]}

Ziegler, Regina G. ^{[3
]}

Berg, Christine D. ^{[15
]}

Buys, Saundra S. ^{[16
]}

McCarty, Catherine A. ^{[17
]}

Feigelson, Heather Spencer ^{[18
]}

Calle, Eugenia E. ^{[18
]}

Thun, Michael J. ^{[18
]}

Diver, W. Ryan ^{[18
]}

Bojesen, Stig ^{[19
,20
]}

Nordestgaard, Borge G. ^{[19
,20
]}

Flyger, Henrik ^{[21
]}

Doerk, Thilo ^{[22
]}

Schuermann, Peter ^{[22
]}

Hillemanns, Peter ^{[22
]}

Karstens, Johann H. ^{[23
]}

Bogdanova, Natalia V. ^{[22
,24
]}

Antonenkova, Natalia N. ^{[24
]}

Zalutsky, Iosif V. ^{[24
]}

Bermisheva, Marina ^{[22
,25
]}

Fedorova, Sardana ^{[26
]}

Khusnutdinova, Elza ^{[25
]}

Kang, Daehee ^{[27
]}

Yoo, Keun-Young ^{[27
]}

Noh, Dong Young ^{[27
]}

Ahn, Sei-Hyun ^{[27
]}

Devilee, Peter ^{[28
,29
]}

van Asperen, Christi J. ^{[30
]}

机构：

[1] Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge, England

[2] Univ Cambridge, Dept Oncol, Cambridge, England

[3] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD USA

[4] Univ Cambridge, EPIC, Dept Publ Hlth & Primary Care, Cambridge, England

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

[6] St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England

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

[8] London Sch Hyg & Trop Med, London WC1, England

[9] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England

[10] Bioinformed Consulting Serv, Gaithersburg, MD USA

[11] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA

[12] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[13] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA

[14] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Pacific Hlth Res Inst, Honolulu, HI 96822 USA

[15] NCI, Canc Prevent Div, NIH, US Dept HHS, Bethesda, MD 20892 USA

[16] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA

[17] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA

[18] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA

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

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

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

[22] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany

[23] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany

[24] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, BELARUS

[25] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450001, Russia

[26] Russian Acad Med Sci, Yakut Res Ctr, Dept Med Genet, Yakutsk, Russia

[27] Seoul Natl Univ, Coll Med, Seoul, South Korea

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

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

[30] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands

[31] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands

[32] Erasmus MC Daniel Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands

[33] M Sklodowska Curie Canc Ctr, Dept Epidemiol & Canc Prevent, Warsaw, Poland

[34] Inst Oncol, Warsaw, Poland

[35] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA

[36] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland

[37] Univ Helsinki, Cent Hosp, Dept Obstet & Gynaecol, Helsinki, Finland

[38] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland

[39] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland

[40] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[41] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia

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

[43] Netherlands Canc Inst, Amsterdam, Netherlands

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

[45] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain

[46] Spanish Natl Canc Res Ctr CNIO, Natl Genotyping Ctr CEGEN, Human Canc Genet Program, Madrid, Spain

[47] Spanish Natl Canc Res Ctr CNIO, Natl Genotyping Ctr CEGEN, Human Canc Genet Program, Madrid, Spain

[48] German Canc Res Ctr, Mol Epidemiol Grp, D-6900 Heidelberg, Germany

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

[50] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany

来源：

NATURE GENETICS | 2009年 / 41卷 / 05期

关键词：

GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS;

D O I：

10.1038/ng.354

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage(1). To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.

引用

页码：585 / 590

页数：6

共 11 条

[1] Differential expression of novel tyrosine kinase substrates during breast cancer development [J].

Chen, Yunhao ;

Choong, Lee-Yee ;

Lin, Qingsong ;

Philp, Robin ;

Wong, Chee-Hong ;

Ang, Boon-Keong ;

Tan, Yee-Ling ;

Loh, Marie-Chiew-Shia ;

Hew, Choy-Leong ;

Shah, Nilesh ;

Druker, Brian J. ;

Chong, Poh-Kuan ;

Lim, Yoon-Pin .

MOLECULAR & CELLULAR PROTEOMICS, 2007, 6 (12) :2072-2087

[2] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[3] 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)

[4] 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

[5] Synip: A novel insulin-regulated syntaxin 4-binding protein mediating GLUT4 translocation in adipocytes [J].

Min, J ;

Okada, S ;

Kanzaki, M ;

Elmendorf, JS ;

Coker, KJ ;

Ceresa, BP ;

Syu, LJ ;

Noda, Y ;

Saltiel, AR ;

Pessin, JE .

MOLECULAR CELL, 1999, 3 (06) :751-760

[6] Caught Nek-ing: cilia and centrioles [J].

Quarmby, LM ;

Mahjoub, MR .

JOURNAL OF CELL SCIENCE, 2005, 118 (22) :5161-5169

[7] Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer [J].

Stacey, Simon N. ;

Manolescu, Andrei ;

Sulem, Patrick ;

Thorlacius, Steinunn ;

Gudjonsson, Sigurjon A. ;

Jonsson, Gudbjorn F. ;

Jakobsdottir, Margret ;

Bergthorsson, Jon T. ;

Gudmundsson, Julius ;

Aben, Katja K. ;

Strobbe, Luc J. ;

Swinkels, Dorine W. ;

van Engelenburg, K. C. Anton ;

Henderson, Brian E. ;

Kolonel, Laurence N. ;

Le Marchand, Loic ;

Millastre, Esther ;

Andres, Raquel ;

Saez, Berta ;

Lambea, Julio ;

Godino, Javier ;

Polo, Eduardo ;

Tres, Alejandro ;

Picelli, Simone ;

Rantala, Johanna ;

Margolin, Sara ;

Jonsson, Thorvaldur ;

Sigurdsson, Helgi ;

Jonsdottir, Thora ;

Hrafnkelsson, Jon ;

Johannsson, Jakob ;

Sveinsson, Thorarinn ;

Myrdal, Gardar ;

Grimsson, Hlynur Niels ;

Sveinsdottir, Steinunn G. ;

Alexiusdottir, Kristin ;

Saemundsdottir, Jona ;

Sigurdsson, Asgeir ;

Kostic, Jelena ;

Gudmundsson, Larus ;

Kristjansson, Kristleifur ;

Masson, Gisli ;

Fackenthal, James D. ;

Adebamowo, Clement ;

Ogundiran, Temidayo ;

Olopade, Olufunmilayo I. ;

Haiman, Christopher A. ;

Lindblom, Annika ;

Mayordomo, Jose I. ;

Kiemeney, Lambertus A. .

NATURE GENETICS, 2008, 40 (06) :703-706

[8] Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer [J].

Stacey, Simon N. ;

Manolescu, Andrei ;

Sulem, Patrick ;

Rafnar, Thorunn ;

Gudmundsson, Julius ;

Gudjonsson, Sigurjon A. ;

Masson, Gisli ;

Jakobsdottir, Margret ;

Thorlacius, Steinunn ;

Helgason, Agnar ;

Aben, Katja K. ;

Strobbe, Luc J. ;

Albers-Akkers, Marjo T. ;

Swinkels, Dorine W. ;

Henderson, Brian E. ;

Kolonel, Laurence N. ;

Le Marchand, Loic ;

Millastre, Esther ;

Andres, Raquel ;

Godino, Javier ;

Garcia-Prats, Maria Dolores ;

Polo, Eduardo ;

Tres, Alejandro ;

Mouy, Magali ;

Saemundsdottir, Jona ;

Backman, Valgerdur M. ;

Gudmundsson, Larus ;

Kristjansson, Kristleifur ;

Bergthorsson, Jon T. ;

Kostic, Jelena ;

Frigge, Michael L. ;

Geller, Frank ;

Gudbjartsson, Daniel ;

Sigurdsson, Helgi ;

Jonsdottir, Thora ;

Hrafnkelsson, Jon ;

Johannsson, Jakob ;

Sveinsson, Thorarinn ;

Myrdal, Gardar ;

Grimsson, Hlynur Niels ;

Jonsson, Thorvaldur ;

von Holst, Susanna ;

Werelius, Barbro ;

Margolin, Sara ;

Lindblom, Annika ;

Mayordomo, Jose I. ;

Haiman, Christopher A. ;

Kiemeney, Lambertus A. ;

Johannsson, Oskar Th ;

Gulcher, Jeffrey R. .

NATURE GENETICS, 2007, 39 (07) :865-869

[9] Population genomics of human gene expression [J].

Stranger, Barbara E. ;

Nica, Alexandra C. ;

Forrest, Matthew S. ;

Dimas, Antigone ;

Bird, Christine P. ;

Beazley, Claude ;

Ingle, Catherine E. ;

Dunning, Mark ;

Flicek, Paul ;

Koller, Daphne ;

Montgomery, Stephen ;

Tavare, Simon ;

Deloukas, Panos ;

Dermitzakis, Emmanouil T. .

NATURE GENETICS, 2007, 39 (10) :1217-1224

[10] The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis [J].

Yin, MJ ;

Shao, LH ;

Voehringer, D ;

Smeal, T ;

Jallal, B .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (52) :52454-52460

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