Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

被引：140

作者：

Broeks, Annegien ^{[1
]}

Schmidt, Marjanka K. ^{[1
,2
]}

Sherman, Mark E. ^{[4
]}

Couch, Fergus J. ^{[5
,6
]}

Hopper, John L. ^{[7
]}

Dite, Gillian S. ^{[7
]}

Apicella, Carmel ^{[7
]}

Smith, Letitia D. ^{[8
]}

Hammet, Fleur ^{[8
]}

Southey, Melissa C. ^{[8
]}

Van 't Veer, Laura J. ^{[1
,3
]}

de Groot, Renate ^{[3
]}

Smit, Vincent T. H. B. M. ^{[9
]}

Fasching, Peter A. ^{[10
]}

Beckmann, Matthias W. ^{[11
]}

Jud, Sebastian ^{[11
]}

Ekici, Arif B. ^{[14
]}

Hartmann, Arndt ^{[12
]}

Hein, Alexander ^{[11
]}

Schulz-Wendtland, Ruediger ^{[13
]}

Burwinkel, Barbara ^{[15
]}

Marme, Frederik ^{[15
]}

Schneeweiss, Andreas ^{[15
]}

Sinn, Hans-Peter ^{[16
]}

Sohn, Christof ^{[15
]}

Tchatchou, Sandrine ^{[15
]}

Bojesen, Stig E. ^{[18
,19
]}

Nordestgaard, Borge G. ^{[18
,19
]}

Flyger, Henrik ^{[18
,19
]}

Orsted, David D. ^{[18
,19
]}

Kaur-Knudsen, Diljit ^{[18
,19
]}

Milne, Roger L. ^{[20
]}

Perez, Jose I. Arias ^{[22
]}

Zamora, Pilar ^{[24
]}

Menendez Rodriguez, Primitiva ^{[23
]}

Benitez, Javier ^{[21
,25
]}

Brauch, Hiltrud ^{[26
,27
]}

Justenhoven, Christina ^{[26
,27
]}

Ko, Yon-Dschun ^{[28
]}

Hamann, Ute ^{[30
]}

Fischer, Hans-Peter ^{[31
]}

Bruening, Thomas ^{[32
]}

Pesch, Beate ^{[32
]}

Chang-Claude, Jenny ^{[17
]}

Wang-Gohrke, Shan ^{[33
]}

Bremer, Michael ^{[34
]}

Karstens, Johann H. ^{[34
]}

Hillemanns, Peter ^{[35
]}

Doerk, Thilo ^{[35
]}

Nevanlinna, Heli A. ^{[36
]}

机构：

[1] Netherlands Canc Inst, Dept Expt Therapy, NL-1066 CX Amsterdam, Netherlands

[2] Netherlands Canc Inst, Dept Epidemiol, NL-1066 CX Amsterdam, Netherlands

[3] Netherlands Canc Inst, Dept Mol Pathol, NL-1066 CX Amsterdam, Netherlands

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

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

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

[7] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia

[8] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic 3010, Australia

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

[10] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

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

[12] Univ Hosp Erlangen, Univ Breast Ctr, Inst Pathol, Erlangen, Germany

[13] Univ Hosp Erlangen, Univ Breast Ctr, Inst Radiol, Erlangen, Germany

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

[15] Univ Heidelberg Hosp, Dept Gynecol & Obstet, Heidelberg, Germany

[16] Univ Heidelberg Hosp, Dept Pathol, Heidelberg, Germany

[17] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany

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

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

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

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

[22] Hosp Monte Naranco, Serv Cirugia Gen, Oviedo, Spain

[23] Hosp Monte Naranco, Serv Anat Patol, Oviedo, Spain

[24] Hosp La Paz, Serv Oncol Med, Madrid, Spain

[25] CIBERER, Madrid, Spain

[26] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany

[27] Univ Tubingen, Tubingen, Germany

[28] Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany

[29] Ruhr Univ Bochum, BGFA Res Inst Occupat Med German Social Accid Ins, Bochum, Germany

[30] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany

[31] Univ Bonn, Fac Med, Inst Pathol, D-5300 Bonn, Germany

[32] Inst Prevent & Occupat Med German Social Accid In, Bochum, Germany

[33] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany

[34] Hannover Med Sch, Clin Radiat Oncol, D-3000 Hannover, Germany

[35] Clin Obstet & Gynaecol, Hannover, Germany

[36] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland

[37] Univ Helsinki, Cent Hosp, Dept Clin Genet, FIN-00290 Helsinki, Finland

[38] Univ Helsinki, Cent Hosp, Dept Pathol, FIN-00290 Helsinki, Finland

[39] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[40] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden

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

[42] Univ Eastern Finland, Inst Clin Med, Dept Pathol, Kuopio, Finland

[43] Kuopio Univ Hosp, SF-70210 Kuopio, Finland

[44] Bioctr Kuopio, Kuopio, Finland

[45] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland

[46] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland

[47] Kuopio Univ Hosp, Dept Surg, SF-70210 Kuopio, Finland

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

[49] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[50] Katholieke Univ Leuven, Vesalius Res Ctr, Leuven, Belgium

来源：

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

基金：

英国医学研究理事会; 芬兰科学院; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; ESTROGEN-RECEPTOR; COMMON VARIANTS; CONFER SUSCEPTIBILITY; RISK; EXPRESSION; PATTERNS; ALLELES; ETIOLOGY;

D O I：

10.1093/hmg/ddr228

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：

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 x 10(-18)), rs3803662 (16q12) (P = 3.7 x 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 x 10(-6) and P = 4.1 x 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P <= 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P <= 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.

引用

页码：3289 / 3303

页数：15

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← 1 2 3 4 →

共 39 条

[1]

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. .

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Althuis MD, 2004, CANCER EPIDEM BIOMAR, V13, P1558

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Anderson, WF ;

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BREAST CANCER RESEARCH AND TREATMENT, 2005, 90 (02) :127-137

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Anderson WF, 2004, CANCER EPIDEM BIOMAR, V13, P1128

[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]

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction [J].

Antoniou, Antonis C. ;

Beesley, Jonathan ;

McGuffog, Lesley ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Neuhausen, Susan L. ;

Ding, Yuan Chun ;

Rebbeck, Timothy R. ;

Weitzel, Jeffrey N. ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Ganz, Patricia A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Couch, Fergus J. ;

Wang, Xianshu ;

Lindor, Noralane M. ;

Pankratz, Vernon S. ;

Radice, Paolo ;

Manoukian, Siranoush ;

Peissel, Bernard ;

Zaffaroni, Daniela ;

Barile, Monica ;

Viel, Alessandra ;

Allavena, Anna ;

Dall'Olio, Valentina ;

Peterlongo, Paolo ;

Szabo, Csilla I. ;

Zikan, Michal ;

Claes, Kathleen ;

Poppe, Bruce ;

Foretova, Lenka ;

Mai, Phuong L. ;

Greene, Mark H. ;

Rennert, Gad ;

Lejbkowicz, Flavio ;

Glendon, Gord ;

Ozcelik, Hilmi ;

Andrulis, Irene L. ;

Thomassen, Mads ;

Gerdes, Anne-Marie ;

Sunde, Lone ;

Cruger, Dorthe ;

Jensen, Uffe Birk ;

Caligo, Maria ;

Friedman, Eitan ;

Kaufman, Bella ;

Laitman, Yael ;

Milgrom, Roni ;

Dubrovsky, Maya .

CANCER RESEARCH, 2010, 70 (23) :9742-9754

[7]

A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population [J].

Antoniou, Antonis C. ;

Wang, Xianshu ;

Fredericksen, Zachary S. ;

McGuffog, Lesley ;

Tarrell, Robert ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Morrison, Jonathan ;

Kartsonaki, Christiana ;

Lesnick, Timothy ;

Ghoussaini, Maya ;

Barrowdale, Daniel ;

Peock, Susan ;

Cook, Margaret ;

Oliver, Clare ;

Frost, Debra ;

Eccles, Diana ;

Evans, D. Gareth ;

Eeles, Ros ;

Izatt, Louise ;

Chu, Carol ;

Douglas, Fiona ;

Paterson, Joan ;

Stoppa-Lyonnet, Dominique ;

Houdayer, Claude ;

Mazoyer, Sylvie ;

Giraud, Sophie ;

Lasset, Christine ;

Remenieras, Audrey ;

Caron, Olivier ;

Hardouin, Agnes ;

Berthet, Pascaline ;

Hogervorst, Frans B. L. ;

Rookus, Matti A. ;

Jager, Agnes ;

van den Ouweland, Ans ;

Hoogerbrugge, Nicoline ;

van der Luijt, Rob B. ;

Meijers-Heijboer, Hanne ;

Garcia, Encarna B. Gomez ;

Devilee, Peter ;

Vreeswijk, Maaike P. G. ;

Lubinski, Jan ;

Jakubowska, Anna ;

Gronwald, Jacek ;

Huzarski, Tomasz ;

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