Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers

被引：23

作者：

Zheng, Yonglan ^{[1
]}

Ogundiran, Temidayo O. ^{[2
]}

Falusi, Adeyinka G. ^{[3
]}

Nathanson, Katherine L. ^{[4
]}

John, Esther M. ^{[5
,6
,7
]}

Hennis, Anselm J. M. ^{[8
,9
]}

Ambs, Stefan ^{[10
]}

Domchek, Susan M. ^{[4
]}

Rebbeck, Timothy R. ^{[11
]}

Simon, Michael S. ^{[12
]}

Nemesure, Barbara ^{[9
]}

Wu, Suh-Yuh ^{[9
]}

Leske, Maria Cristina ^{[9
]}

Odetunde, Abayomi ^{[3
]}

Niu, Qun ^{[1
]}

Zhang, Jing ^{[1
]}

Afolabi, Chibuzor ^{[2
]}

Gamazon, Eric R. ^{[13
]}

Cox, Nancy J. ^{[13
]}

Olopade, Christopher O. ^{[1
]}

Olopade, Olufunmilayo I. ^{[1
]}

Huo, Dezheng ^{[14
]}

机构：

[1] Univ Chicago, Dept Med, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA

[2] Univ Ibadan, Coll Med, Dept Surg, Ibadan 23402, Oyo, Nigeria

[3] Univ Ibadan, Coll Med, Inst Med Res & Training, Ibadan 23402, Oyo, Nigeria

[4] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[5] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA

[6] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA

[7] Stanford Univ, Stanford Canc Inst, Div Epidemiol, Sch Med, Stanford, CA 94305 USA

[8] Univ W Indies, Res Inst Trop Med, Chron Dis Res Ctr, BB-11000 Bridgetown, Saint Michael, Barbados

[9] SUNY Stony Brook, Med Ctr, Dept Prevent Med, Stony Brook, NY 11794 USA

[10] NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[11] Univ Penn, Dept Stat & Epidemiol, Philadelphia, PA 19104 USA

[12] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48201 USA

[13] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA

[14] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA

来源：

CARCINOGENESIS | 2013年 / 34卷 / 07期

关键词：

BRCA1 MUTATION CARRIERS; COMMON VARIANTS; CONFER SUSCEPTIBILITY; TERT-CLPTM1L LOCUS; RISK VARIANT; AMERICAN; FGFR2; POLYMORPHISMS; REPLICATION; ADMIXTURE;

D O I：

10.1093/carcin/bgt090

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.111.76; P 0.004), 5q11.2 (OR 1.22, 95% CI 1.091.36; P 0.00053) and 10p15.1 (OR 1.22, 95% CI 1.081.38; P 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR 1.21, 95% CI 1.161.27; P 9.7 10(16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

引用

页码：1520 / 1528

页数：9

共 51 条

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Ziegler, Regina G. ;

Deming, Sandra L. ;

Bandera, Elisa V. ;

Nyante, Sarah ;

Palmer, Julie R. ;

Rebbeck, Timothy R. ;

Ingles, Sue A. ;

Press, Michael F. ;

Rodriguez-Gil, Jorge L. ;

Chanock, Stephen J. ;

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← 1 2 3 4 5 6 →

共 51 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] 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-+

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Banerji, Shantanu ;

Cibulskis, Kristian ;

Rangel-Escareno, Claudia ;

Brown, Kristin K. ;

Carter, Scott L. ;

Frederick, Abbie M. ;

Lawrence, Michael S. ;

Sivachenko, Andrey Y. ;

Sougnez, Carrie ;

Zou, Lihua ;

Cortes, Maria L. ;

Fernandez-Lopez, Juan C. ;

Peng, Shouyong ;

Ardlie, Kristin G. ;

Auclair, Daniel ;

Bautista-Pina, Veronica ;

Duke, Fujiko ;

Francis, Joshua ;

Jung, Joonil ;

Maffuz-Aziz, Antonio ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Pho, Nam H. ;

Quintanar-Jurado, Valeria ;

Ramos, Alex H. ;

Rebollar-Vega, Rosa ;

Rodriguez-Cuevas, Sergio ;

Romero-Cordoba, Sandra L. ;

Schumacher, Steven E. ;

Stransky, Nicolas ;

Thompson, Kristin M. ;

Uribe-Figueroa, Laura ;

Baselga, Jose ;

Beroukhim, Rameen ;

Polyak, Kornelia ;

Sgroi, Dennis C. ;

Richardson, Andrea L. ;

Jimenez-Sanchez, Gerardo ;

Lander, Eric S. ;

Gabriel, Stacey B. ;

Garraway, Levi A. ;

Golub, Todd R. ;

Melendez-Zajgla, Jorge ;

Toker, Alex ;

Getz, Gad ;

Hidalgo-Miranda, Alfredo ;

Meyerson, Matthew .

NATURE, 2012, 486 (7403) :405-409

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Barnholtz-Sloan, Jill S. ;

Shetty, Priya B. ;

Guan, Xiaowei ;

Nyante, Sarah J. ;

Luo, Jingchun ;

Brennan, Donal J. ;

Millikan, Robert C. .

CARCINOGENESIS, 2010, 31 (08) :1417-1423

[5] Association of breast cancer outcome with status of p53 and MDM2 SNP309 [J].

Boersma, Brenda J. ;

Howe, Tiffany M. ;

Goodman, Julie E. ;

Yfantis, Harry G. ;

Lee, Dong H. ;

Chanock, Stephen J. ;

Ambs, Stefan .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2006, 98 (13) :911-919

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Cai, Qiuyin ;

Long, Jirong ;

Lu, Wei ;

Qu, Shimian ;

Wen, Wanqing ;

Kang, Daehee ;

Lee, Ji-Young ;

Chen, Kexin ;

Shen, Hongbing ;

Shen, Chen-Yang ;

Sung, Hyuna ;

Matsuo, Keitaro ;

Haiman, Christopher A. ;

Khoo, Ui Soon ;

Ren, Zefang ;

Iwasaki, Motoki ;

Gu, Kai ;

Xiang, Yong-Bing ;

Choi, Ji-Yeob ;

Park, Sue K. ;

Zhang, Lina ;

Hu, Zhibin ;

Wu, Pei-Ei ;

Noh, Dong-Young ;

Tajima, Kazuo ;

Henderson, Brian E. ;

Chan, Kelvin Y. K. ;

Su, Fengxi ;

Kasuga, Yoshio ;

Wang, Wenjing ;

Cheng, Jia-Rong ;

Yoo, Keun-Young ;

Lee, Jong-Young ;

Zheng, Hong ;

Liu, Yao ;

Shieh, Ya-Lan ;

Kim, Sung-Won ;

Lee, Jong Won ;

Iwata, Hiroji ;

Le Marchand, Loic ;

Chan, Sum Yin ;

Xie, Xiaoming ;

Tsugane, Shoichiro ;

Lee, Min Hyuk ;

Wang, Shenming ;

Li, Guoliang ;

Levy, Shawn ;

Huang, Bo ;

Shi, Jiajun ;

Delahanty, Ryan .

HUMAN MOLECULAR GENETICS, 2011, 20 (24) :4991-4999

[7] Replication and Functional Genomic Analyses of the Breast Cancer Susceptibility Locus at 6q25.1 Generalize Its Importance in Women of Chinese, Japanese, and European Ancestry [J].

Cai, Qiuyin ;

Wen, Wanqing ;

Qu, Shimian ;

Li, Guoliang ;

Egan, Kathleen M. ;

Chen, Kexin ;

Deming, Sandra L. ;

Shen, Hongbing ;

Shen, Chen-Yang ;

Gammon, Marilie D. ;

Blot, William J. ;

Matsuo, Keitaro ;

Haiman, Christopher A. ;

Khoo, Ui Soon ;

Iwasaki, Motoki ;

Santella, Regina M. ;

Zhang, Lina ;

Fair, Alecia Malin ;

Hu, Zhibin ;

Wu, Pei-Ei ;

Signorello, Lisa B. ;

Titus-Ernstoff, Linda ;

Tajima, Kazuo ;

Henderson, Brian E. ;

Chan, Kelvin Y. K. ;

Kasuga, Yoshio ;

Newcomb, Polly A. ;

Zheng, Hong ;

Cui, Yong ;

Wang, Furu ;

Shieh, Ya-Lan ;

Iwata, Hiroji ;

Le Marchand, Loic ;

Chan, Sum Yin ;

Shrubsole, Martha J. ;

Trentham-Dietz, Amy ;

Tsugane, Shoichiro ;

Garcia-Closas, Montserrat ;

Long, Jirong ;

Li, Chun ;

Shi, Jiajun ;

Huang, Bo ;

Xiang, Yong-Bing ;

Gao, Yu-Tang ;

Lu, Wei ;

Shu, Xiao-Ou ;

Zheng, Wei .

CANCER RESEARCH, 2011, 71 (04) :1344-1355

[8] Replicating genotype-phenotype associations [J].

Chanock, Stephen J. ;

Manolio, Teri ;

Boehnke, Michael ;

Boerwinkle, Eric ;

Hunter, David J. ;

Thomas, Gilles ;

Hirschhorn, Joel N. ;

Abecasis, Goncalo ;

Altshuler, David ;

Bailey-Wilson, Joan E. ;

Brooks, Lisa D. ;

Cardon, Lon R. ;

Daly, Mark ;

Donnelly, Peter ;

Fraumeni, Joseph F., Jr. ;

Freimer, Nelson B. ;

Gerhard, Daniela S. ;

Gunter, Chris ;

Guttmacher, Alan E. ;

Guyer, Mark S. ;

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