Genome-wide association analysis identifies three new breast cancer susceptibility loci

被引：214

作者：

Ghoussaini, Maya ^{[1
]}

Fletcher, Olivia ^{[2
]}

Michailidou, Kyriaki ^{[3
]}

Turnbull, Clare ^{[4
]}

Schmidt, Marjanka K. ^{[5
,6
]}

Dicks, Ed ^{[1
]}

Dennis, Joe ^{[3
]}

Wang, Qin ^{[3
]}

Humphreys, Manjeet K. ^{[3
]}

Luccarini, Craig ^{[1
]}

Baynes, Caroline ^{[1
]}

Conroy, Don ^{[1
]}

Maranian, Melanie ^{[1
]}

Ahmed, Shahana ^{[1
]}

Driver, Kristy ^{[1
]}

Johnson, Nichola ^{[2
]}

Orr, Nicholas ^{[2
]}

Silva, Isabel dos Santos ^{[7
]}

Waisfisz, Quinten ^{[8
]}

Meijers-Heijboer, Hanne ^{[8
]}

Uitterlinden, Andre G. ^{[9
]}

Rivadeneira, Fernando ^{[9
]}

Hall, Per ^{[10
]}

Czene, Kamila ^{[10
]}

Irwanto, Astrid ^{[11
,12
]}

Liu, Jianjun ^{[13
]}

Nevanlinna, Heli ^{[11
,12
]}

Aittomaki, Kristiina ^{[12
,14
]}

Blomqvist, Carl ^{[12
,15
]}

Meindl, Alfons ^{[16
]}

Schmutzler, Rita K. ^{[17
]}

Mueller-Myhsok, Bertram ^{[18
]}

Lichtner, Peter ^{[19
]}

Chang-Claude, Jenny ^{[20
]}

Hein, Rebecca ^{[20
,21
]}

Nickels, Stefan ^{[20
]}

Flesch-Janys, Dieter ^{[22
,23
]}

Tsimiklis, Helen ^{[24
]}

Makalic, Enes ^{[25
]}

Schmidt, Daniel ^{[25
]}

Bui, Minh ^{[25
]}

Hopper, John L. ^{[25
]}

Apicella, Carmel ^{[25
]}

Park, Daniel J. ^{[24
]}

Southey, Melissa ^{[24
]}

Hunter, David J. ^{[26
]}

Chanock, Stephen J. ^{[27
]}

Broeks, Annegien ^{[5
]}

Verhoef, Senno ^{[28
]}

Hogervorst, Frans B. L. ^{[29
]}

机构：

[1] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[2] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

[3] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[4] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[5] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands

[6] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands

[7] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England

[8] Vrije Univ Amsterdam Med Ctr, Sect Oncogenet, Dept Clin Genet, Amsterdam, Netherlands

[9] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands

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

[11] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland

[12] Univ Helsinki, Cent Hosp, Helsinki, Finland

[13] Genome Inst Singapore, Human Genet Div, Singapore, Singapore

[14] Univ Helsinki, Dept Clin Genet, Helsinki, Finland

[15] Univ Helsinki, Dept Oncol, Helsinki, Finland

[16] Tech Univ Munich, Div Gynaecol Tumor Genet, Clin Gynaecol & Obstet, Munich, Germany

[17] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaecooncol, D-50931 Cologne, Germany

[18] Max Planck Inst Psychiat, D-80804 Munich, Germany

[19] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[20] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, D-6900 Heidelberg, Germany

[21] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, Primar Med Versorgung PMV Res Grp, D-50931 Cologne, Germany

[22] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany

[23] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany

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

[25] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[26] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA

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

[28] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Clin Genet, Amsterdam, Netherlands

[29] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Mol Pathol, Amsterdam, Netherlands

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

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

[32] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Div Canc Studies, Natl Inst Hlth Res NIHR Comprehens Biomed Res Ctr, London, England

[33] Kings Coll London, Div Canc Studies, London WC2R 2LS, England

[34] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England

[35] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[36] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland

[37] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[38] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany

[39] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany

[40] Ctr Rech Epidemiol & Populat Hlth CESP, INSERM, U1018, Villejuif, France

[41] Univ Paris 11, Unite Mixte Rech Sante UMRS 1018, Villejuif, France

[42] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark

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

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

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

[46] CNIO, Human Canc Genet Programme, Human Genotyping Unit, Madrid, Spain

[47] CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain

[48] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA

[49] City Hope Canc Ctr, Duarte, CA USA

[50] Canc Prevent Inst Calif, Fremont, CA USA

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HORMONE-RELATED PROTEIN; PARATHYROID-HORMONE; NEGATIVE-FEEDBACK; COMMON VARIANTS; CONFER SUSCEPTIBILITY; GENE-EXPRESSION; CELL CARCINOMA; RETINOIC ACID; MAMMARY-GLAND; RECEPTOR;

D O I：

10.1038/ng.1049

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

引用

页码：312 / U120

页数：8

共 67 条

[61] Negative feedback at the level of nuclear receptor coregulation - Self-limitation of retinoid signaling by RIP140 [J].

White, KA ;

Yore, MM ;

Warburton, SL ;

Vaseva, AV ;

Rieder, E ;

Freemantle, SJ ;

Spinella, MJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (45) :43889-43892

[62] Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations [J].

Wu, Chen ;

Hu, Zhibin ;

He, Zhonghu ;

Jia, Weihua ;

Wang, Feng ;

Zhou, Yifeng ;

Liu, Zhihua ;

Zhan, Qimin ;

Liu, Yu ;

Yu, Dianke ;

Zhai, Kan ;

Chang, Jiang ;

Qiao, Yan ;

Jin, Guangfu ;

Liu, Zhe ;

Shen, Yuanyuan ;

Guo, Chuanhai ;

Fu, Jianhua ;

Miao, Xiaoping ;

Tan, Wen ;

Shen, Hongbing ;

Ke, Yang ;

Zeng, Yixin ;

Wu, Tangchun ;

Lin, Dongxin .

NATURE GENETICS, 2011, 43 (07) :679-U97

[63] The physiology of parathyroid hormone-related protein: An emerging role as a developmental factor [J].

Wysolmerski, JJ ;

Stewart, AF .

ANNUAL REVIEW OF PHYSIOLOGY, 1998, 60 :431-460

[64] HYPERCALCEMIA OF MALIGNANCY - THE CENTRAL ROLE OF PARATHYROID HORMONE-RELATED PROTEIN [J].

WYSOLMERSKI, JJ ;

BROADUS, AE .

ANNUAL REVIEW OF MEDICINE, 1994, 45 :189-200

[65] Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation [J].

Wysolmerski, John J. .

SKELETAL BIOLOGY AND MEDICINE, 2010, 1192 :161-169

[66] Significance of the parathyroid hormone-related protein expression in breast carcinoma [J].

Yoshida A. ;

Nakamura Y. ;

Shimizu A. ;

Harada M. ;

Kameda Y. ;

Nagano A. ;

Inaba M. ;

Asaga T. .

Breast Cancer, 2000, 7 (3) :215-220

[67] Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1 [J].

Zheng, Wei ;

Long, Jirong ;

Gao, Yu-Tang ;

Li, Chun ;

Zheng, Ying ;

Xiang, Yong-Bin ;

Wen, Wanqing ;

Levy, Shawn ;

Deming, Sandra L. ;

Haines, Jonathan L. ;

Gu, Kai ;

Fair, Alecia Malin ;

Cai, Qiuyin ;

Lu, Wei ;

Shu, Xiao-Ou .

NATURE GENETICS, 2009, 41 (03) :324-328

← 1 2 3 4 5 6 7 →