Genome-wide association study identifies five new breast cancer susceptibility loci.
Breast cancer is the most common cancer in women in developed countries. To identify common breast cancer susceptibility alleles, we conducted a genome-wide association study in which 582,886 SNPs were genotyped in 3,659 cases with a family history of the disease and 4,897 controls. Promising associations were evaluated in a second stage, comprising 12,576 cases and 12,223 controls. We identified five new susceptibility loci, on chromosomes 9, 10 and 11 (P = 4.6 x 10(-7) to P = 3.2 x 10(-15)). We also identified SNPs in the 6q25.1 (rs3757318, P = 2.9 x 10(-6)), 8q24 (rs1562430, P = 5.8 x 10(-7)) and LSP1 (rs909116, P = 7.3 x 10(-7)) regions that showed more significant association with risk than those reported previously. Previously identified breast cancer susceptibility loci were also found to show larger effect sizes in this study of familial breast cancer cases than in previous population-based studies, consistent with polygenic susceptibility to the disease.
Turnbull
Clare
C
Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey, UK.
Ahmed
Shahana
S
Morrison
Jonathan
J
Pernet
David
D
Renwick
Anthony
A
Maranian
Mel
M
Seal
Sheila
S
Ghoussaini
Maya
M
Hines
Sarah
S
Healey
Catherine S
CS
Hughes
Deborah
D
Warren-Perry
Margaret
M
Tapper
William
W
Eccles
Diana
D
Evans
D Gareth
DG
Hooning
Maartje
M
Schutte
Mieke
M
van den Ouweland
Ans
A
Houlston
Richard
R
Ross
Gillian
G
Langford
Cordelia
C
Pharoah
Paul D P
PD
Stratton
Michael R
MR
Dunning
Alison M
AM
Rahman
Nazneen
N
Easton
Douglas F
DF
D001943:Breast Neoplasms / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide
Genes Chromosomes Cancer. 1994 Jan;9(1):42-8
7507699
PLoS One. 2009;4(4):e5027
19343170
Nat Genet. 2009 Aug;41(8):899-904
19578367
Int J Epidemiol. 2006 Feb;35(1):34-41
16155052
Nat Genet. 2007 Mar;39(3):352-8
17293864
Nature. 2007 Jun 28;447(7148):1087-93
17529967
Nat Genet. 2007 Jul;39(7):870-4
17529973
Genet Epidemiol. 2003 Nov;25(3):190-202
14557987
Nat Genet. 2009 May;41(5):585-90
19330027
J Natl Cancer Inst. 2009 Jul 15;101(14):1012-8
19567422
Science. 2007 Jun 1;316(5829):1336-41
17463249
Nat Genet. 2009 Aug;41(8):905-8
19578366
Am J Hum Genet. 2002 Feb;70(2):425-34
11791212
Nat Genet. 2008 Jun;40(6):703-6
18438407
Nat Genet. 2008 Aug;40(8):955-62
18587394
Science. 1994 Apr 15;264(5157):436-40
8153634
Nat Genet. 2009 May;41(5):579-84
19330030
Nat Genet. 2009 Mar;41(3):324-8
19219042
Nat Genet. 2007 Jul;39(7):865-9
17529974
Bioinformatics. 2007 Oct 15;23(20):2741-6
17846035
Nat Genet. 2009 Aug;41(8):909-14
19578363
Nature. 2007 Jun 7;447(7145):661-78
17554300
Nat Genet. 2009 Aug;41(8):915-9
19578365
Nat Genet. 2009 Aug;41(8):920-5
19578364
J Biol Chem. 1996 Jun 21;271(25):15292-7
8663044
Nat Genet. 1994 Sep;8(1):23-6
7987388
Bioinformatics. 2007 May 15;23(10):1294-6
17384015
Nat Genet. 2006 Aug;38(8):904-9
16862161
Am J Hum Genet. 2003 Jun;72(6):1479-91
12740763
Hum Mol Genet. 2009 May 1;18(9):1692-703
19223389