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Genome-wide association study identifies novel breast cancer susceptibility loci

Easton, D.F.; Pooley, K.A.; Dunning, A.M.; Pharoah, P.D.P.; Thompson, D.; Ballinger, D.G.; Struewing, J.P.; Morrison, J.; Field, H.; Luben, R.; Wareham, N.; Ahmed, S.; Healey, C.S.; Bowman, R.; Meyer, K.B.; Haiman, C.A.; Kolonel, L.K.; Henderson, B.E.; le Marchand, L.; Brennan, P.; Sangrajrang, S.; Gaborieau, V.; Odefrey, F.; Shen, C.Y.; Wu, P.E.; Wang, H.C.; Eccles, D.; Evans, D.G.; Peto, J.; Fletcher, O.; Johnson, N.; Seal, S.; Stratton, M.R.; Rahman, N.; Chenevix-Trench, G.; Bojesen, S.E.; Nordestgaard, B.G.; Axelsson, C.K.; Garcia-Closas, M.; Brinton, L.; Chanock, S.; Lissowska, J.; Peplonska, B.; Nevanlinna, H.; Fagerholm, R.; Eerola, H.; Kang, D.; Yoo, K.Y.; Noh, D.Y.; Ahn, S.H.; Hunter, D.J.; Hankinson, S.E.; Cox, D.G.; Hall, P.; Wedren, S.; Liu, J.J.; Low, Y.L.; Bogdanova, N.; Schurmann, P.; Dork, T.; Tollenaar, R.; Jacobi, C.E.; Devilee, P.; Klijn, J.G.M.; Sigurdson, A.J.; Doody, M.M.; Alexander, B.H.; Zhang, J.H.; Cox, A.; Brock, I.W.; MacPherson, G.; Reed, M.W.R.; Couch, F.J.; Goode, E.L.; Olson, J.E.; Meijers-Heijboer, H.; van Den Ouweland, A.; Uitterlinden, A.; Rivadeneira, F.; Milne, R.L.; Ribas, G.; Gonzalez-Neira, A.; Benitez, J.; Hopper, J.L.; McCredie, M.; Southey, M.; Giles, G.G.; Schroen, C.; Justenhoven, C.; Brauch, H.; Hamann, U.; Ko, Y.D.; Spurdle, A.B.; Beesley, J.; Chen, X.Q.; Mannermaa, A.; Kosma, V.M.; Kataja, V.; Hartikainen, J.; Day, N.E.; Cox, D.R.; Ponder, B.A.J.
Nature, 2007; 447(7148):1087-U7
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pub_id
17529967
pubmedid
17529967
ISI
247564600032
reference_type
Journal Article
author
Easton, D.F.; Pooley, K.A.; Dunning, A.M.; Pharoah, P.D.P.; Thompson, D.; Ballinger, D.G.; Struewing, J.P.; Morrison, J.; Field, H.; Luben, R.; Wareham, N.; Ahmed, S.; Healey, C.S.; Bowman, R.; Meyer, K.B.; Haiman, C.A.; Kolonel, L.K.; Henderson, B.E.; le Marchand, L.; Brennan, P.; Sangrajrang, S.; Gaborieau, V.; Odefrey, F.; Shen, C.Y.; Wu, P.E.; Wang, H.C.; Eccles, D.; Evans, D.G.; Peto, J.; Fletcher, O.; Johnson, N.; Seal, S.; Stratton, M.R.; Rahman, N.; Chenevix-Trench, G.; Bojesen, S.E.; Nordestgaard, B.G.; Axelsson, C.K.; Garcia-Closas, M.; Brinton, L.; Chanock, S.; Lissowska, J.; Peplonska, B.; Nevanlinna, H.; Fagerholm, R.; Eerola, H.; Kang, D.; Yoo, K.Y.; Noh, D.Y.; Ahn, S.H.; Hunter, D.J.; Hankinson, S.E.; Cox, D.G.; Hall, P.; Wedren, S.; Liu, J.J.; Low, Y.L.; Bogdanova, N.; Schurmann, P.; Dork, T.; Tollenaar, R.; Jacobi, C.E.; Devilee, P.; Klijn, J.G.M.; Sigurdson, A.J.; Doody, M.M.; Alexander, B.H.; Zhang, J.H.; Cox, A.; Brock, I.W.; MacPherson, G.; Reed, M.W.R.; Couch, F.J.; Goode, E.L.; Olson, J.E.; Meijers-Heijboer, H.; van Den Ouweland, A.; Uitterlinden, A.; Rivadeneira, F.; Milne, R.L.; Ribas, G.; Gonzalez-Neira, A.; Benitez, J.; Hopper, J.L.; McCredie, M.; Southey, M.; Giles, G.G.; Schroen, C.; Justenhoven, C.; Brauch, H.; Hamann, U.; Ko, Y.D.; Spurdle, A.B.; Beesley, J.; Chen, X.Q.; Mannermaa, A.; Kosma, V.M.; Kataja, V.; Hartikainen, J.; Day, N.E.; Cox, D.R.; Ponder, B.A.J.
title
Genome-wide association study identifies novel breast cancer susceptibility loci
secondary_title
Nature
ISBNISSN
0028-0836
volume
447
number
7148
pages
1087-U7
year
2007
abstract
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.
keywords
GROWTH-FACTOR RECEPTOR-2; OVARIAN-CANCER; BRCA2 MUTATIONS; GENE; CHEK2-ASTERISK-1100DELC; POPULATIONS; PATTERNS; DATABASE; DISEASE; VARIANT
secondary_author
place_published
publisher
number_of_volumes
tertiary_author
tertiary_title
edition
date
Jun
type_of_work
Article
subsidiary_author
alternate_title
Nature
call_number
accession_number
17529967
custom_1
WOS OK
custom_2
860
custom_3
custom_4
10.1038/nature05887
custom_5
custom_6
10
label
notes
ISI Document Delivery No.: 183HT Times Cited: 0 Cited Reference Count: 40
url
://000247564600032 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17529967
author_address
Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England. Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia. Univ Otago, Dept Prevent & Social Med, Dunedin 9001, New Zealand. Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia. Spanish Natl Canc Ctr CNIO, E-28029 Madrid, Spain. Erasmus Univ, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands. Mayo Clin, Coll Med, Rochester, MN 55905 USA. Univ Sheffield, Sch Med, Acad Unit Surg Oncol, Sheffield S10 2RX, S Yorkshire, England. Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield S10 2RX, S Yorkshire, England. Univ Minnesota, Minneapolis, MN 55455 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Dept Med Oncol, Family Canc Clin, NL-3075 EA Rotterdam, Netherlands. Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Med Decis Making, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Surg, NL-2333 ZA Leiden, Netherlands. Hannover Med Sch, Dept Obstet & Gynecol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany. Genome Inst Singapore, Singapore 138672, Singapore. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Univ Ulsan, Coll Med, Ulsan 680749, South Korea. Natl Canc Ctr, Goyang 411769, South Korea. Seoul Natl Univ, Coll Med, Seoul 151742, South Korea. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki 00029, Finland. Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki 00029, Finland. Nofer Inst Occupat Med, PL-90950 Lodz, Poland. M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. Ctr Canc, PL-02781 Warsaw, Poland. NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Copenhagen, Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. Univ Copenhagen, Bispebjerg Univ Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. Breakthrought Breast Canc Res Ctr, London SW3 6JB, England. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. Princess Anne Hosp, Wessex Clin Genet Serv, Southampton SO16 5YA, Hants, England. Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan. NCI, Bangkok 10400, Thailand. Int Agcy Res Canc, F-69008 Lyon, France. Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. Univ Calif Los Angeles, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. MRC, Dunn Clin Nutr Ctr, Cambridge CB2 0XY, England. Univ Cambridge, Dept Publ Hlth & Primary Care, EPIC, Cambridge CB1 8RN, England. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Perlegen Sci Inc, Mountain View, CA 94043 USA. Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. Vaasa Cent Hosp, Dept Oncol, Vaasa 65130, Finland. Kuopio Univ Hosp, Dept Oncol, FIN-70211 Kuopio, Finland. Kuopio Univ Hosp, Dept Pathol, FIN-70211 Kuopio, Finland. Univ Kuopio, Inst Clin Med Pathol & Forens Med, FIN-70210 Kuopio, Finland. Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. Evangel Kliniken Bonn GGmbh, Johanniter Krankenhaus, D-53113 Bonn, Germany. Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. Univ Tubingen, D-72074 Tubingen, Germany. Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. Easton, DF, Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. d.easton@srl.cam.ac.uk
library
nature05887 10.1038/nature05887 17529967
created
2007-07-17 10:23:22
modified
2012-03-12 20:20:06
library

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