Genome-wide association study identifies novel breast cancer susceptibility loci

被引：1747

作者：

Easton, Douglas F. ^{[1
]}

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

Fletcher, Olivia

Johnson, Nichola

Seal, Sheila

Stratton, Michael R.

Rahman, Nazneen

Chenevix-Trench, Georgia

Bojesen, Stig E.

Nordestgaard, Borge G.

Axelsson, Christen K.

Garcia-Closas, Montserrat

Brinton, Louise

Chanock, Stephen

Lissowska, Jolanta

Peplonska, Beata

Nevanlinna, Heli

Fagerholm, Rainer

Eerola, Hannaleena

Kang, Daehee

Yoo, Keun-Young

Noh, Dong-Young

Ahn, Sei-Hyun

机构：

[1] Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge CB1 8RN, England

[2] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England

[3] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia

[4] Univ Otago, Dept Prevent & Social Med, Dunedin 9001, New Zealand

[5] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia

[6] Spanish Natl Canc Ctr CNIO, E-28029 Madrid, Spain

[7] Erasmus Univ, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands

[8] Mayo Clin, Coll Med, Rochester, MN 55905 USA

[9] Univ Sheffield, Sch Med, Acad Unit Surg Oncol, Sheffield S10 2RX, S Yorkshire, England

[10] Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield S10 2RX, S Yorkshire, England

[11] Univ Minnesota, Minneapolis, MN 55455 USA

[12] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA

[13] Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Dept Med Oncol, Family Canc Clin, NL-3075 EA Rotterdam, Netherlands

[14] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands

[15] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZA Leiden, Netherlands

[16] Leiden Univ, Med Ctr, Dept Med Decis Making, NL-2333 ZA Leiden, Netherlands

[17] Leiden Univ, Med Ctr, Dept Surg, NL-2333 ZA Leiden, Netherlands

[18] Hannover Med Sch, Dept Obstet & Gynecol, D-30625 Hannover, Germany

[19] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany

[20] Genome Inst Singapore, Singapore 138672, Singapore

[21] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

[22] Harvard Univ, Sch Med, Boston, MA 02115 USA

[23] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA

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

[25] Univ Ulsan, Coll Med, Ulsan 680749, South Korea

[26] Natl Canc Ctr, Goyang 411769, South Korea

[27] Seoul Natl Univ, Coll Med, Seoul 151742, South Korea

[28] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki 00029, Finland

[29] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki 00029, Finland

[30] Nofer Inst Occupat Med, PL-90950 Lodz, Poland

[31] M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland

[32] Ctr Canc, PL-02781 Warsaw, Poland

[33] NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA

[34] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA

[35] Univ Copenhagen, Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark

[36] Univ Copenhagen, Bispebjerg Univ Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark

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

[38] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England

[39] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England

[40] Breakthrought Breast Canc Res Ctr, London SW3 6JB, England

[41] Inst Canc Res, Sutton SM2 5NG, Surrey, England

[42] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England

[43] St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England

[44] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton SO16 5YA, Hants, England

[45] Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan

[46] NCI, Bangkok 10400, Thailand

[47] Int Agcy Res Canc, F-69008 Lyon, France

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

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

[50] MRC, Dunn Clin Nutr Ctr, Cambridge CB2 0XY, England

来源：

NATURE | 2007年 / 447卷 / 7148期

关键词：

D O I：

10.1038/nature05887

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r(2) > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.

引用

页码：1087 / U7

页数：9

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