Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

被引：56

作者：

Antoniou, Antonis C. ^{[1
]}

Kartsonaki, Christiana

Sinilnikova, Olga M. ^{[3
,4
]}

Soucy, Penny

McGuffog, Lesley

Healey, Sue ^{[6
]}

Lee, Andrew

Peterlongo, Paolo ^{[8
,10
]}

Manoukian, Siranoush ^{[9
]}

Peissel, Bernard ^{[9
]}

Zaffaroni, Daniela ^{[9
]}

Cattaneo, Elisa ^{[9
]}

Barile, Monica ^{[11
]}

Pensotti, Valeria ^{[12
]}

Pasini, Barbara ^{[13
]}

Dolcetti, Riccardo ^{[14
]}

Giannini, Giuseppe ^{[15
]}

Putignano, Anna Laura ^{[16
,17
]}

Varesco, Liliana ^{[18
]}

Radice, Paolo ^{[8
]}

Mai, Phuong L. ^{[19
]}

Greene, Mark H. ^{[19
]}

Andrulis, Irene L. ^{[20
,21
,22
,23
]}

Glendon, Gord ^{[23
]}

Ozcelik, Hilmi ^{[20
,22
]}

Thomassen, Mads ^{[24
]}

Gerdes, Anne-Marie ^{[25
]}

Kruse, Torben A. ^{[24
]}

Jensen, Uffe Birk ^{[26
]}

Crueger, Dorthe G. ^{[27
]}

Caligo, Maria A. ^{[28
,29
]}

Laitman, Yael ^{[30
]}

Milgrom, Roni ^{[30
]}

Kaufman, Bella ^{[31
]}

Paluch-Shimon, Shani ^{[31
]}

Friedman, Eitan ^{[30
]}

Loman, Niklas ^{[32
]}

Harbst, Katja ^{[32
]}

Lindblom, Annika ^{[33
]}

Arver, Brita ^{[34
]}

Ehrencrona, Hans ^{[35
]}

Melin, Beatrice ^{[36
]}

Nathanson, Katherine L. ^{[37
]}

Domchek, Susan M. ^{[37
]}

Rebbeck, Timothy ^{[37
]}

Jakubowska, Ania ^{[38
]}

Lubinski, Jan ^{[38
]}

Gronwald, Jacek ^{[38
]}

Huzarski, Tomasz ^{[38
]}

Byrski, Tomasz ^{[38
]}

机构：

[1] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England

[2] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England

[3] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France

[4] Univ Lyon, Ctr Leon Berard, CNRS, Equipe Labellisee LIGUE 2008,UMR5201, Lyon, France

[5] Ctr Hosp Univ Quebec, Canc Genom Lab, Canada Res Chair Oncogenet, Quebec City, PQ, Canada

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

[7] Peter MacCallum Canc Ctr, kConFab Kathleen Cuningham Consortium Res Familial, Melbourne, Vic, Australia

[8] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy

[9] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predicted Med, Unit Med Genet, Milan, Italy

[10] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy

[11] IEO, Div Canc Prevent & Genet, Milan, Italy

[12] Cogentech, Consortium Genom Technol, Milan, Italy

[13] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy

[14] IRCCS, Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Aviano, PN, Italy

[15] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy

[16] Univ Florence, Dept Clin Physiopathol, Florence, Italy

[17] Fiorgen Fdn Pharmacogen, Sesto Fiorentino, Italy

[18] Ist Nazl Ric Canc IST, Dept Epidemiol Prevent & Special Funct, Unit Hereditary Canc, Genoa, Italy

[19] US Natl Canc Inst, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA

[20] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[21] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[22] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[23] Canc Care Ontario, Toronto, ON, Canada

[24] Odense Univ Hosp, DK-5000 Odense C, Denmark

[25] Rigshosp, DK-2100 Copenhagen, Denmark

[26] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark

[27] Vejle Hosp, Vejle, Denmark

[28] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy

[29] Univ Hosp Pisa, Pisa, Italy

[30] Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Tel Hashomer, Israel

[31] Sheba Med Ctr, Inst Oncol, Breast Canc Unit, Tel Hashomer, Israel

[32] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden

[33] Karolinska Univ Hosp, Dept Clin Genet, S-17176 Stockholm, Sweden

[34] Karolinska Univ Hosp, Dept Oncol, S-17176 Stockholm, Sweden

[35] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, S-75185 Uppsala, Sweden

[36] Umea Univ, Dept Radiat Sci, S-90185 Umea, Sweden

[37] Univ Penn, Philadelphia, PA 19104 USA

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

[39] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain

[40] Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Spain

[41] Natl Ctr Sci Res Demokritos, IRRP, Mol Diagnost Lab, Athens, Greece

[42] Hosp Clin Univ Lozano Blesa, Oncol unit, Zaragoza, Spain

[43] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany

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

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

[46] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands

[47] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet 849, NL-6525 ED Nijmegen, Netherlands

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

[49] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands

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

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 16期

关键词：

GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; CONFER SUSCEPTIBILITY; GENETIC MODIFIERS; VARIANTS; LOCUS; 2Q35;

D O I：

10.1093/hmg/ddr226

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

引用

页码：3304 / 3321

页数：18

共 44 条

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← 1 2 3 4 5 →

共 44 条

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

Ahmed, Shahana ;

Thomas, Gilles ;

Ghoussaini, Maya ;

Healey, Catherine S. ;

Humphreys, Manjeet K. ;

Platte, Radka ;

Morrison, Jonathan ;

Maranian, Melanie ;

Pooley, Karen A. ;

Luben, Robert ;

Eccles, Diana ;

Evans, D. Gareth ;

Fletcher, Olivia ;

Johnson, Nichola ;

Silva, Isabel dos Santos ;

Peto, Julian ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Jacobs, Kevin ;

Prentice, Ross ;

Anderson, Garnet L. ;

Rajkovic, Aleksandar ;

Curb, J. David ;

Ziegler, Regina G. ;

Berg, Christine D. ;

Buys, Saundra S. ;

McCarty, Catherine A. ;

Feigelson, Heather Spencer ;

Calle, Eugenia E. ;

Thun, Michael J. ;

Diver, W. Ryan ;

Bojesen, Stig ;

Nordestgaard, Borge G. ;

Flyger, Henrik ;

Doerk, Thilo ;

Schuermann, Peter ;

Hillemanns, Peter ;

Karstens, Johann H. ;

Bogdanova, Natalia V. ;

Antonenkova, Natalia N. ;

Zalutsky, Iosif V. ;

Bermisheva, Marina ;

Fedorova, Sardana ;

Khusnutdinova, Elza ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong Young ;

Ahn, Sei-Hyun ;

Devilee, Peter ;

van Asperen, Christi J. .

NATURE GENETICS, 2009, 41 (05) :585-590

[2]

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Ali, S ;

Coombes, RC .

NATURE REVIEWS CANCER, 2002, 2 (02) :101-+

[3]

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions [J].

Antoniou, A. C. ;

Cunningham, A. P. ;

Peto, J. ;

Evans, D. G. ;

Lalloo, F. ;

Narod, S. A. ;

Risch, H. A. ;

Eyfjord, J. E. ;

Hopper, J. L. ;

Southey, M. C. ;

Olsson, H. ;

Johannsson, O. ;

Borg, A. ;

Passini, B. ;

Radice, P. ;

Manoukian, S. ;

Eccles, D. M. ;

Tang, N. ;

Olah, E. ;

Anton-Culver, H. ;

Warner, E. ;

Lubinski, J. ;

Gronwald, J. ;

Gorski, B. ;

Tryggvadottir, L. ;

Syrjakoski, K. ;

Kallioniemi, O-P ;

Eerola, H. ;

Nevanlinna, H. ;

Pharoah, P. D. P. ;

Easton, D. F. .

BRITISH JOURNAL OF CANCER, 2008, 98 (08) :1457-1466

[4]

A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes [J].

Antoniou, AC ;

Goldgar, DE ;

Andrieu, N ;

Chang-Claude, J ;

Brohet, R ;

Rookus, MA ;

Easton, DF .

GENETIC EPIDEMIOLOGY, 2005, 29 (01) :1-11

[5]

Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers [J].

Antoniou, Antonis C. ;

Spurdle, Amanda B. ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Pooley, Karen A. ;

Schmutzler, Rita K. ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Arnold, Norbert ;

Hofmann, Wera ;

Sutter, Christian ;

Niederacher, Dieter ;

Deissler, Helmut ;

Caldes, Trinidad ;

Kampjarvi, Kati ;

Nevanlinna, Heli ;

Simard, Jacques ;

Beesley, Jonathan ;

Chen, Xiaoqing ;

Neuhausen, Susan L. ;

Rebbeck, Timothy R. ;

Wagner, Theresa ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Weitzel, Jeffrey ;

Ganz, Patricia A. ;

Daly, Mary B. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Bium, Joanne L. ;

Couch, Fergus J. ;

Peterlongo, Paolo ;

Manoukian, Siranoush ;

Barile, Monica ;

Radice, Paolo ;

Szabo, Csilla I. ;

Pereira, Lutecia H. Mateus ;

Greene, Mark H. ;

Rennert, Gad ;

Leibkowicz, Flavio ;

Barnett-Griness, Ofra ;

Andrulis, Irene L. ;

Ozcelik, Hilmi ;

Gerdes, Anne-Marie ;

Caligo, Maria A. ;

Laitman, Yael ;

Kaufman, Bella ;

Milgrom, Roni ;

Friedman, Eitan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (04) :937-948

[6]

RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers:: Results from a combined analysis of 19 studies [J].

Antoniou, Antonis C. ;

Sinilnikova, Olga M. ;

Simard, Jacques ;

Leone, Melanie ;

Dumont, Martine ;

Neuhausen, Susan L. ;

Struewing, Jeffery P. ;

Stoppa-Lyonnet, Dominique ;

Barjhoux, Laure ;

Hughes, David J. ;

Coupier, Isabelle ;

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