Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans

被引：53

作者：

Chen, Fang ^{[3
]}

Chen, Gary K. ^{[3
]}

Millikan, Robert C. ^{[4
,5
]}

John, Esther M. ^{[6
,7
,8
]}

Ambrosone, Christine B. ^{[9
]}

Bernstein, Leslie ^{[10
]}

Zheng, Wei ^{[11
,12
]}

Hu, Jennifer J. ^{[13
,14
]}

Ziegler, Regina G. ^{[15
]}

Deming, Sandra L. ^{[11
,12
]}

Bandera, Elisa V. ^{[16
]}

Nyante, Sarah ^{[4
,5
]}

Palmer, Julie R. ^{[17
]}

Rebbeck, Timothy R. ^{[18
]}

Ingles, Sue A. ^{[3
]}

Press, Michael F. ^{[1
,2
]}

Rodriguez-Gil, Jorge L. ^{[13
,14
]}

Chanock, Stephen J. ^{[15
]}

Le Marchand, Loic ^{[19
]}

Kolonel, Laurence N. ^{[19
]}

Henderson, Brian E. ^{[3
]}

Stram, Daniel O. ^{[3
]}

Haiman, Christopher A. ^{[3
]}

机构：

[1] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA

[2] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA

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

[4] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[6] No Calif Canc Ctr, Fremont, CA USA

[7] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[8] Stanford Univ, Stanford Canc Ctr, Stanford, CA 94305 USA

[9] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA

[10] Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, City Of Hope, CA USA

[11] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA

[12] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA

[13] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[14] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA

[15] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[16] Canc Inst New Jersey, New Brunswick, NJ USA

[17] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA

[18] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[19] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 22期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; COMMON VARIANTS; CONFER SUSCEPTIBILITY; PROTEIN HZIMP10; MULTIPLE LOCI; 8Q24; POLYMORPHISMS; EPIDEMIOLOGY; COACTIVATOR; REPLICATION;

D O I：

10.1093/hmg/ddr367

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genome-wide association studies (GWAS) have revealed 19 common genetic variants that are associated with breast cancer risk. Testing of the index signals found through GWAS and fine-mapping of each locus in diverse populations will be necessary for characterizing the role of these risk regions in contributing to inherited susceptibility. In this large study of breast cancer in African-American women (3016 cases and 2745 controls), we tested the 19 known risk variants identified by GWAS and replicated associations (P < 0.05) with only 4 variants. Through fine-mapping, we identified markers in four regions that better capture the association with breast cancer risk in African Americans as defined by the index signal (2q35, 5q11, 10q26 and 19p13). We also identified statistically significant associations with markers in four separate regions (8q24, 10q22, 11q13 and 16q12) that are independent of the index signals and may represent putative novel risk variants. In aggregate, the more informative markers found in the study enhance the association of these risk regions with breast cancer in African Americans [per allele odds ratio (OR) 5 1.18, P = 2.8 3 10(-24) versus OR =1.04, P = 6.1 x 10(-5)]. In this detailed analysis of the known breast cancer risk loci, we have validated and improved upon markers of risk that better characterize their association with breast cancer in women of African ancestry.

引用

页码：4491 / 4503

页数：13

共 55 条

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Le Marchand, Loic ;

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Haiman, Christopher A. .

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← 1 2 3 4 5 6 →

共 55 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. .

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

[2] Multiple loci on 8q24 associated with prostate cancer susceptibility [J].

Al Olama, Ali Amin ;

Kote-Jarai, Zsofia ;

Giles, Graham G. ;

Guy, Michelle ;

Morrison, Jonathan ;

Severi, Gianluca ;

Leongamornlert, Daniel A. ;

Tymrakiewicz, Malgorzata ;

Jhavar, Sameer ;

Saunders, Ed ;

Hopper, John L. ;

Southey, Melissa C. ;

Muir, Kenneth R. ;

English, Dallas R. ;

Dearnaley, David P. ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Wilkinson, Rosemary A. ;

Sawyer, Emma ;

Lophatananon, Artitaya ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

Cooper, Colin ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Neal, David E. ;

Eeles, Rosalind A. ;

Easton, Douglas F. .

NATURE GENETICS, 2009, 41 (10) :1058-1060

[3] Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women [J].

Ambrosone, Christine B. ;

Ciupak, Gregory L. ;

Bandera, Elisa V. ;

Jandorf, Lina ;

Bovbjerg, Dana H. ;

Zirpoli, Gary ;

Pawlish, Karen ;

Godbold, James ;

Furberg, Helena ;

Fatone, Anne ;

Valdimarsdottir, Heiddis ;

Yao, Song ;

Li, Yulin ;

Hwang, Helena ;

Davis, Warren ;

Roberts, Michelle ;

Sucheston, Lara ;

Demissie, Kitaw ;

Amend, Kandace L. ;

Tartter, Paul ;

Reilly, James ;

Pace, Benjamin W. ;

Rohan, Thomas ;

Sparano, Joseph ;

Raptis, George ;

Castaldi, Maria ;

Estabrook, Alison ;

Feldman, Sheldon ;

Weltz, Christina ;

Kemeny, Margaret .

JOURNAL OF ONCOLOGY, 2009, 2009

[4] 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 ;

Byrski, Tomasz ;

Gorski, Bohdan ;

Cybulski, Cezary ;

Spurdle, Amanda B. .

NATURE GENETICS, 2010, 42 (10) :885-+

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

Broeks, Annegien ;

Schmidt, Marjanka K. ;

Sherman, Mark E. ;

Couch, Fergus J. ;

Hopper, John L. ;

Dite, Gillian S. ;

Apicella, Carmel ;

Smith, Letitia D. ;

Hammet, Fleur ;

Southey, Melissa C. ;

Van 't Veer, Laura J. ;

de Groot, Renate ;

Smit, Vincent T. H. B. M. ;

Fasching, Peter A. ;

Beckmann, Matthias W. ;

Jud, Sebastian ;

Ekici, Arif B. ;

Hartmann, Arndt ;

Hein, Alexander ;

Schulz-Wendtland, Ruediger ;

Burwinkel, Barbara ;

Marme, Frederik ;

Schneeweiss, Andreas ;

Sinn, Hans-Peter ;

Sohn, Christof ;

Tchatchou, Sandrine ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Flyger, Henrik ;

Orsted, David D. ;

Kaur-Knudsen, Diljit ;

Milne, Roger L. ;

Perez, Jose I. Arias ;

Zamora, Pilar ;

Menendez Rodriguez, Primitiva ;

Benitez, Javier ;

Brauch, Hiltrud ;

Justenhoven, Christina ;

Ko, Yon-Dschun ;

Hamann, Ute ;

Fischer, Hans-Peter ;

Bruening, Thomas ;

Pesch, Beate ;

Chang-Claude, Jenny ;

Wang-Gohrke, Shan ;

Bremer, Michael ;

Karstens, Johann H. ;

Hillemanns, Peter ;

Doerk, Thilo ;

Nevanlinna, Heli A. .

HUMAN MOLECULAR GENETICS, 2011, 20 (16) :3289-3303

[6] Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations [J].

Chen, Fang ;

Stram, Daniel O. ;

Le Marchand, Loic ;

Monroe, Kristine R. ;

Kolonel, Laurence N. ;

Henderson, Brian E. ;

Haiman, Christopher A. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2011, 19 (02) :243-245

[7] Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk [J].

Crowther-Swanepoel, Dalemari ;

Broderick, Peter ;

Di Bernardo, Maria Chiara ;

Dobbins, Sara E. ;

Torres, Maria ;

Mansouri, Mahmoud ;

Ruiz-Ponte, Clara ;

Enjuanes, Anna ;

Rosenquist, Richard ;

Carracedo, Angel ;

Jurlander, Jesper ;

Campo, Elias ;

Juliusson, Gunnar ;

Montserrat, Emilio ;

Smedby, Karin E. ;

Dyer, Martin J. S. ;

Matutes, Estella ;

Dearden, Claire ;

Sunter, Nicola J. ;

Hall, Andrew G. ;

Mainou-Fowler, Tryfonia ;

Jackson, Graham H. ;

Summerfield, Geoffrey ;

Harris, Robert J. ;

Pettitt, Andrew R. ;

Allsup, David J. ;

Bailey, James R. ;

Pratt, Guy ;

Pepper, Chris ;

Fegan, Chris ;

Parker, Anton ;

Oscier, David ;

Allan, James M. ;

Catovsky, Daniel ;

Houlston, Richard S. .

NATURE GENETICS, 2010, 42 (02) :132-U59

[8] 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 ;

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