Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci

被引：32

作者：

Han, Mi-Ryung ^{[1
]}

Long, Jirong ^{[1
]}

Choi, Ji-Yeob ^{[2
,3
]}

Low, Siew-Kee ^{[4
]}

Kweon, Sun-Seog ^{[5
,6
]}

Zheng, Ying ^{[7
]}

Cai, Qiuyin ^{[1
]}

Shi, Jiajun ^{[1
]}

Guo, Xingyi ^{[1
]}

Matsuo, Keitaro ^{[8
,9
]}

Iwasaki, Motoki ^{[10
]}

Shen, Chen-Yang ^{[11
,12
,13
]}

Kim, Mi Kyung ^{[14
]}

Wen, Wanqing ^{[1
]}

Li, Bingshan ^{[15
]}

Takahashi, Atsushi ^{[4
]}

Shin, Min-Ho ^{[5
]}

Xiang, Yong-Bing ^{[16
]}

Ito, Hidemi ^{[17
]}

Kasuga, Yoshio ^{[18
]}

Noh, Dong-Young ^{[3
,19
]}

Matsuda, Koichi ^{[20
]}

Park, Min Ho ^{[21
]}

Gao, Yu-Tang

Iwata, Hiroji ^{[22
]}

Tsugane, Shoichiro ^{[23
]}

Park, Sue K. ^{[2
,3
,24
]}

Kubo, Michiaki ^{[25
]}

Shu, Xiao-Ou ^{[1
]}

Kang, Daehee ^{[2
,3
,24
]}

Zheng, Wei ^{[1
]}

机构：

[1] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med,Div Epidemiol,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA

[2] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 03080, South Korea

[3] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 03080, South Korea

[4] RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa 3510198, Japan

[5] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwangju 61469, South Korea

[6] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun 58128, South Korea

[7] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai 200336, Peoples R China

[8] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi 4648681, Japan

[9] Nagoya Univ, Grad Sch Med, Dept Epidemiol, Nagoya, Aichi 4648681, Japan

[10] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol Div, Tokyo 1040045, Japan

[11] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan

[12] Acad Sinica, Taiwan Biobank, Taipei 115, Taiwan

[13] China Med Univ, Coll Publ Hlth, Taichung 404, Taiwan

[14] Natl Canc Ctr, Div Canc Epidemiol & Management, Gyeonggi Do 10408, South Korea

[15] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

[16] Shanghai Canc Inst, Dept Epidemiol, Shanghai 200032, Peoples R China

[17] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4648681, Japan

[18] Nagano Matsushiro Gen Hosp, Dept Surg, Nagano 3811231, Japan

[19] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 03080, South Korea

[20] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med, Tokyo 1088639, Japan

[21] Chonnam Natl Univ, Sch Med, Dept Surg, Gwangju 61469, South Korea

[22] Aichi Canc Ctr, Cent Hosp, Dept Breast Oncol, Nagoya, Aichi 4648681, Japan

[23] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Tokyo 1040045, Japan

[24] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 03080, South Korea

[25] RIKEN, Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa 3510198, Japan

来源：

HUMAN MOLECULAR GENETICS | 2016年 / 25卷 / 15期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

RISK VARIANT; CONFER SUSCEPTIBILITY; COMMON VARIANTS; TRANSGENIC MICE; GENE; EXPRESSION; GENOTYPE; METAANALYSIS; LMO4; STRATIFICATION;

D O I：

10.1093/hmg/ddw164

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：

Breast cancer is one of the most common malignancies among women worldwide. Genetic factors have been shown to play an important role in breast cancer aetiology. We conducted a two-stage genome-wide association study (GWAS) including 14 224 cases and 14 829 controls of East Asian women to search for novel genetic susceptibility loci for breast cancer. Single nucleotide polymorphisms (SNPs) in two loci were found to be associated with breast cancer risk at the genome-wide significance level. The first locus, represented by rs12118297 at 1p22.3 (near the LMO4 gene), was associated with breast cancer risk with odds ratio (OR) and (95% confidence interval (CI)) of 0.91 (0.88-0.94) and a P-value of 4.48 x 10 (8). This association was replicated in another study, DRIVE GAME-ON Consortium, including 16 003 cases and 41 335 controls of European ancestry (OR = 0.95, 95% CI - 0.91-0.99, P-value - 0.019). The second locus, rs16992204 at 21q22.12 (near the LINC00160 gene), was associated with breast cancer risk with OR (95% CI) of 1.13 (1.07-1.18) and a P-value of 4.63 x 10 (8). The risk allele frequency for this SNP is zero in European-ancestry populations in 1000 Genomes Project and thus its association with breast cancer risk cannot be assessed in DRIVE GAME-ON Consortium. Functional annotation using the ENCODE data indicates that rs12118297 might be located in a repressed element and locus 21q22.12 may affect breast cancer risk through regulating LINC00160 expressions and interaction with oestrogen receptor signalling. Our findings provide additional insights into the genetics of breast cancer.

引用

页码：3361 / 3371

页数：11

共 87 条

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← 1 2 3 4 5 6 7 8 9 →

共 87 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 ;

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Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

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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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Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

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BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

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Boyle, Alan P. ;

Hong, Eurie L. ;

Hariharan, Manoj ;

Cheng, Yong ;

Schaub, Marc A. ;

Kasowski, Maya ;

Karczewski, Konrad J. ;

Park, Julie ;

Hitz, Benjamin C. ;

Weng, Shuai ;

Cherry, J. Michael ;

Snyder, Michael .

GENOME RESEARCH, 2012, 22 (09) :1790-1797

[7] Runx1 Is Associated With Breast Cancer Progression in MMTV-PyMT Transgenic Mice and its Depletion In Vitro Inhibits Migration and Invasion [J].

Browne, Gillian ;

Taipaleenmaeki, Hanna ;

Bishop, Nicole M. ;

Madasu, Sharath C. ;

Shaw, Leslie M. ;

Van Wijnen, Andre J. ;

Stein, Janet L. ;

Stein, Gary S. ;

Lian, Jane B. .

JOURNAL OF CELLULAR PHYSIOLOGY, 2015, 230 (10) :2522-2532

[8] Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1 [J].

Cai, Qiuyin ;

Zhang, Ben ;

Sung, Hyuna ;

Low, Siew-Kee ;

Kweon, Sun-Seog ;

Lu, Wei ;

Shi, Jiajun ;

Long, Jirong ;

Wen, Wanqing ;

Choi, Ji-Yeob ;

Noh, Dong-Young ;

Shen, Chen-Yang ;

Matsuo, Keitaro ;

Teo, Soo-Hwang ;

Kim, Mi Kyung ;

Khoo, Ui Soon ;

Iwasaki, Motoki ;

Hartman, Mikael ;

Takahashi, Atsushi ;

Ashikawa, Kyota ;

Matsuda, Koichi ;

Shin, Min-Ho ;

Park, Min Ho ;

Zheng, Ying ;

Xiang, Yong-Bing ;

Ji, Bu-Tian ;

Park, Sue K. ;

Wu, Pei-Ei ;

Hsiung, Chia-Ni ;

Ito, Hidemi ;

Kasuga, Yoshio ;

Kang, Peter ;

Mariapun, Shivaani ;

Ahn, Sei Hyun ;

Kang, Han Sung ;

Chan, Kelvin Y. K. ;

Man, Ellen P. S. ;

Iwata, Hiroji ;

Tsugane, Shoichiro ;

Miao, Hui ;

Liao, Jiemin ;

Nakamura, Yusuke ;

Kubo, Michiaki ;

Delahanty, Ryan J. ;

Zhang, Yanfeng ;

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