Genome-wide association study identifies novel breast cancer susceptibility loci

Douglas F. Easton; Karen A. Pooley; Alison M. Dunning; Paul D.P. Pharoah; Deborah Thompson; Dennis G. Ballinger; Jeffery P. Struewing; Jonathan Morrison; Helen Field; Robert Luben; Nicholas Wareham; Shahana Ahmed; Catherine S. Healey; Richard Bowman; The SEARCH Collaborators; Kerstin B. Meyer; Christopher A. Haiman; Laurence K. Kolonel; Brian E. Henderson; Loic Le Marchand; Paul Brennan; Suleeporn Sangrajrang; Valerie Gaborieau; Fabrice Odefrey; Chen-Yang Shen; Pei-Ei Wu; Hui-Chun Wang; Diana Eccles; D. Gareth Evans; Julian Peto; Olivia Fletcher; Nichola Johnson; Sheila Seal; Michael R. Stratton; Nazneen Rahman; Georgia Chenevix-Trench; Stig E. Bojesen; Børge G. Nordestgaard; Christen K. Axelsson; Montserrat Garcia-Closas; Louise Brinton; Stephen Chanock; Jolanta Lissowska; Beata Peplonska; Heli Nevanlinna; Rainer Fagerholm; Hannaleena Eerola; Daehee Kang; Keun-Young Yoo; Dong-Young Noh; Sei-Hyun Ahn; David J. Hunter; Susan E. Hankinson; David G. Cox; Per Hall; Sara Wedren; Jianjun Liu; Yen-Ling Low; Natalia Bogdanova; Peter Schürmann; Thilo Dörk; Rob A.E.M. Tollenaar; Catharina E. Jacobi; Peter Devilee; Jan G.M. Klijn; Alice J. Sigurdson; Michele M. Doody; Bruce H. Alexander; Jinghui Zhang; Angela Cox; Gordon MacPherson; Malcolm W.R. Reed; Fergus J. Couch; Ellen L. Goode; Janet E. Olson; Hanne Meijers-Heijboer; Ans Van Den Ouweland; André Uitterlinden; Fernando Rivadeneira; Roger L. Milne; Gloria Ribas; Anna Gonzalez-Neira; Javier Benitez; John L. Hopper; Margaret McCredie; Melissa Southey; Graham G. Giles; Chris Schroen; Christina Justenhoven; Hiltrud Brauch; Ute Hamann; Yon-Dschun Ko; Amanda B. Spurdle; Jonathan Beesley; Xiaoqing Chen; kConFab; AOCS Management Group; Arto Mannermaa; Veli Matti Kosma; Vesa Kataja; Jaana Hartikainen; Nicholas E. Day; David R. Cox; Bruce A.J. Ponder; Frank Firgaira; Scott Grist; Eric Haan; Ram Seshadri

doi:10.1038/nature05887

Genome-wide association study identifies novel breast cancer susceptibility loci

Douglas F. Easton, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Deborah Thompson, Dennis G. Ballinger, Jeffery P. Struewing, Jonathan Morrison, Helen Field, Robert Luben, Nicholas Wareham, Shahana Ahmed, Catherine S. Healey, Richard Bowman, The SEARCH Collaborators, Kerstin B. Meyer, Christopher A. Haiman, Laurence K. Kolonel, Brian E. Henderson, Loic Le MarchandPaul Brennan, Suleeporn Sangrajrang, Valerie Gaborieau, Fabrice Odefrey, Chen-Yang Shen, Pei-Ei Wu, Hui-Chun Wang, Diana Eccles, D. Gareth Evans, Julian Peto, Olivia Fletcher, Nichola Johnson, Sheila Seal, Michael R. Stratton, Nazneen Rahman, Georgia Chenevix-Trench, Stig E. Bojesen, Børge G. Nordestgaard, Christen K. Axelsson, Montserrat Garcia-Closas, Louise Brinton, Stephen Chanock, Jolanta Lissowska, Beata Peplonska, Heli Nevanlinna, Rainer Fagerholm, Hannaleena Eerola, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, David J. Hunter, Susan E. Hankinson, David G. Cox, Per Hall, Sara Wedren, Jianjun Liu, Yen-Ling Low, Natalia Bogdanova, Peter Schürmann, Thilo Dörk, Rob A.E.M. Tollenaar, Catharina E. Jacobi, Peter Devilee, Jan G.M. Klijn, Alice J. Sigurdson, Michele M. Doody, Bruce H. Alexander, Jinghui Zhang, Angela Cox, Gordon MacPherson, Malcolm W.R. Reed, Fergus J. Couch, Ellen L. Goode, Janet E. Olson, Hanne Meijers-Heijboer, Ans Van Den Ouweland, André Uitterlinden, Fernando Rivadeneira, Roger L. Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, John L. Hopper, Margaret McCredie, Melissa Southey, Graham G. Giles, Chris Schroen, Christina Justenhoven, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, kConFab, AOCS Management Group, Arto Mannermaa, Veli Matti Kosma, Vesa Kataja, Jaana Hartikainen, Nicholas E. Day, David R. Cox, Bruce A.J. Ponder, Frank Firgaira, Scott Grist, Eric Haan, Ram Seshadri

Research output: Contribution to journal › Article › peer-review

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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 r²> 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.

Original language	English
Pages (from-to)	1087-1093
Number of pages	7
Journal	Nature
Volume	447
DOIs	https://doi.org/10.1038/nature05887
Publication status	Published - 28 Jun 2007
Externally published	Yes

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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., The SEARCH Collaborators, Meyer, K. B., Haiman, C. A., Kolonel, L. K., Henderson, B. E., ... Seshadri, R. (2007). Genome-wide association study identifies novel breast cancer susceptibility loci. Nature, 447, 1087-1093. https://doi.org/10.1038/nature05887

@article{c113afc6684242a49c35d76d9ba9789b,

title = "Genome-wide association study identifies novel breast cancer susceptibility loci",

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 r2> 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.",

author = "Easton, {Douglas F.} and Pooley, {Karen A.} and Dunning, {Alison M.} and Pharoah, {Paul D.P.} and Deborah Thompson and Ballinger, {Dennis G.} and Struewing, {Jeffery P.} and Jonathan Morrison and Helen Field and Robert Luben and Nicholas Wareham and Shahana Ahmed and Healey, {Catherine S.} and Richard Bowman and {The SEARCH Collaborators} and Meyer, {Kerstin B.} and Haiman, {Christopher A.} and Kolonel, {Laurence K.} and Henderson, {Brian E.} and {Le Marchand}, Loic and Paul Brennan and Suleeporn Sangrajrang and Valerie Gaborieau and Fabrice Odefrey and Chen-Yang Shen and Pei-Ei Wu and Hui-Chun Wang and Diana Eccles and Evans, {D. Gareth} and Julian Peto and Olivia Fletcher and Nichola Johnson and Sheila Seal and Stratton, {Michael R.} and Nazneen Rahman and Georgia Chenevix-Trench and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Axelsson, {Christen K.} and Montserrat Garcia-Closas and Louise Brinton and Stephen Chanock and Jolanta Lissowska and Beata Peplonska and Heli Nevanlinna and Rainer Fagerholm and Hannaleena Eerola and Daehee Kang and Keun-Young Yoo and Dong-Young Noh and Sei-Hyun Ahn and Hunter, {David J.} and Hankinson, {Susan E.} and Cox, {David G.} and Per Hall and Sara Wedren and Jianjun Liu and Yen-Ling Low and Natalia Bogdanova and Peter Sch{\"u}rmann and Thilo D{\"o}rk and Tollenaar, {Rob A.E.M.} and Jacobi, {Catharina E.} and Peter Devilee and Klijn, {Jan G.M.} and Sigurdson, {Alice J.} and Doody, {Michele M.} and Alexander, {Bruce H.} and Jinghui Zhang and Angela Cox and Brock, {Ian W.} and Gordon MacPherson and Reed, {Malcolm W.R.} and Couch, {Fergus J.} and Goode, {Ellen L.} and Olson, {Janet E.} and Hanne Meijers-Heijboer and {Van Den Ouweland}, Ans and Andr{\'e} Uitterlinden and Fernando Rivadeneira and Milne, {Roger L.} and Gloria Ribas and Anna Gonzalez-Neira and Javier Benitez and Hopper, {John L.} and Margaret McCredie and Melissa Southey and Giles, {Graham G.} and Chris Schroen and Christina Justenhoven and Hiltrud Brauch and Ute Hamann and Yon-Dschun Ko and Spurdle, {Amanda B.} and Jonathan Beesley and Xiaoqing Chen and kConFab and {AOCS Management Group} and Arto Mannermaa and Kosma, {Veli Matti} and Vesa Kataja and Jaana Hartikainen and Day, {Nicholas E.} and Cox, {David R.} and Ponder, {Bruce A.J.} and Craig Luccarini and Don Conroy and Mitul Shah and Hannah Munday and Clare Jordan and Barbara Perkins and Judy West and Karen Redman and Kristy Driver and Morteza Aghmesheh and David Amor and Lesley Andrews and Yoland Antill and Jane Armes and Shane Armitage and Leanne Arnold and Rosemary Balleine and Glenn Begley and John Beilby and Ian Bennett and Barbara Bennett and Geoffrey Berry and Anneke Blackburn and Meagan Brennan and Melissa Brown and Michael Buckley and Jo Burke and Phyllis Butow and Keith Byron and David Callen and Ian Campbell and Christine Clarke and Alison Colley and Dick Cotton and Jisheng Cui and Bronwyn Culling and Margaret Cummings and Dawson, {Sarah Jane} and Joanne Dixon and Alexander Dobrovic and Tracy Dudding and Ted Edkins and Maurice Eisenbruch and Gelareh Farshid and Susan Fawcett and Michael Field and Frank Firgaira and Jean Fleming and John Forbes and Michael Friedlander and Clara Gaff and Mac Gardner and Mike Gattas and Peter George and Grantley Gill and Jack Goldblatt and Sian Greening and Scott Grist and Eric Haan and Marion Harris and Stewart Hart and Nick Hayward and John Hopper and Evelyn Humphrey and Mark Jenkins and Alison Jones and Rick Kefford and Judy Kirk and James Kollias and Sergey Kovalenko and Sunil Lakhani and Jennifer Leary and Jacqueline Lim and Geoff Lindeman and Lara Lipton and Liz Lobb and Mariette Maclurcan and Graham Mann and Deborah Marsh and Michael McKay and {Anne McLachlan}, Sue and Bettina Meiser and Roger Milne and Gillian Mitchell and Beth Newman and Imelda O'Loughlin and Richard Osborne and Lester Peters and Kelly Phillips and Melanie Price and Jeanne Reeve and Tony Reeve and Robert Richards and Gina Rinehart and Bridget Robinson and Barney Rudzki and Elizabeth Salisbury and Joe Sambrook and Christobel Saunders and Clare Scott and Elizabeth Scott and Rodney Scott and Ram Seshadri and Andrew Shelling and Amanda Spurdle and Graeme Suthers and Donna Taylor and Christopher Tennant and Heather Thorne and Sharron Townshend and Kathy Tucker and Janet Tyler and Deon Venter and Jane Visvader and Ian Walpole and Robin Ward and Paul Waring and Bev Warner and Graham Warren and Elizabeth Watson and Rachael Williams and Judy Wilson and Ingrid Winship and Young, {Mary Ann} and David Bowtell and Adele Green and Anna deFazio and Dorota Gertig and Penny Webb",

year = "2007",

month = jun,

day = "28",

doi = "10.1038/nature05887",

language = "English",

volume = "447",

pages = "1087--1093",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

}

Easton, DF, Pooley, KA, Dunning, AM, Pharoah, PDP, Thompson, D, Ballinger, DG, Struewing, JP, Morrison, J, Field, H, Luben, R, Wareham, N, Ahmed, S, Healey, CS, Bowman, R, The SEARCH Collaborators, Meyer, KB, Haiman, CA, Kolonel, LK, Henderson, BE, Le Marchand, L, Brennan, P, Sangrajrang, S, Gaborieau, V, Odefrey, F, Shen, C-Y, Wu, P-E, Wang, H-C, Eccles, D, Evans, DG, Peto, J, Fletcher, O, Johnson, N, Seal, S, Stratton, MR, Rahman, N, Chenevix-Trench, G, Bojesen, SE, Nordestgaard, BG, Axelsson, CK, 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, DJ, Hankinson, SE, Cox, DG, Hall, P, Wedren, S, Liu, J, Low, Y-L, Bogdanova, N, Schürmann, P, Dörk, T, Tollenaar, RAEM, Jacobi, CE, Devilee, P, Klijn, JGM, Sigurdson, AJ, Doody, MM, Alexander, BH, Zhang, J, Cox, A, MacPherson, G, Reed, MWR, Couch, FJ, Goode, EL, Olson, JE, Meijers-Heijboer, H, Van Den Ouweland, A, Uitterlinden, A, Rivadeneira, F, Milne, RL, Ribas, G, Gonzalez-Neira, A, Benitez, J, Hopper, JL, McCredie, M, Southey, M, Giles, GG, Schroen, C, Justenhoven, C, Brauch, H, Hamann, U, Ko, Y-D, Spurdle, AB, Beesley, J, Chen, X, kConFab, AOCS Management Group, Mannermaa, A, Kosma, VM, Kataja, V, Hartikainen, J, Day, NE, Cox, DR, Ponder, BAJ, Firgaira, F, Grist, S, Haan, E & Seshadri, R 2007, 'Genome-wide association study identifies novel breast cancer susceptibility loci', Nature, vol. 447, pp. 1087-1093. https://doi.org/10.1038/nature05887

TY - JOUR

T1 - Genome-wide association study identifies novel breast cancer susceptibility loci

AU - Easton, Douglas F.

AU - Pooley, Karen A.

AU - Dunning, Alison M.

AU - Pharoah, Paul D.P.

AU - Thompson, Deborah

AU - Ballinger, Dennis G.

AU - Struewing, Jeffery P.

AU - Morrison, Jonathan

AU - Field, Helen

AU - Luben, Robert

AU - Wareham, Nicholas

AU - Ahmed, Shahana

AU - Healey, Catherine S.

AU - Bowman, Richard

AU - The SEARCH Collaborators

AU - Meyer, Kerstin B.

AU - Haiman, Christopher A.

AU - Kolonel, Laurence K.

AU - Henderson, Brian E.

AU - Le Marchand, Loic

AU - Brennan, Paul

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Odefrey, Fabrice

AU - Shen, Chen-Yang

AU - Wu, Pei-Ei

AU - Wang, Hui-Chun

AU - Eccles, Diana

AU - Evans, D. Gareth

AU - Peto, Julian

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Seal, Sheila

AU - Stratton, Michael R.

AU - Rahman, Nazneen

AU - Chenevix-Trench, Georgia

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Axelsson, Christen K.

AU - Garcia-Closas, Montserrat

AU - Brinton, Louise

AU - Chanock, Stephen

AU - Lissowska, Jolanta

AU - Peplonska, Beata

AU - Nevanlinna, Heli

AU - Fagerholm, Rainer

AU - Eerola, Hannaleena

AU - Kang, Daehee

AU - Yoo, Keun-Young

AU - Noh, Dong-Young

AU - Ahn, Sei-Hyun

AU - Hunter, David J.

AU - Hankinson, Susan E.

AU - Cox, David G.

AU - Hall, Per

AU - Wedren, Sara

AU - Liu, Jianjun

AU - Low, Yen-Ling

AU - Bogdanova, Natalia

AU - Schürmann, Peter

AU - Dörk, Thilo

AU - Tollenaar, Rob A.E.M.

AU - Jacobi, Catharina E.

AU - Devilee, Peter

AU - Klijn, Jan G.M.

AU - Sigurdson, Alice J.

AU - Doody, Michele M.

AU - Alexander, Bruce H.

AU - Zhang, Jinghui

AU - Cox, Angela

AU - Brock, Ian W.

AU - MacPherson, Gordon

AU - Reed, Malcolm W.R.

AU - Couch, Fergus J.

AU - Goode, Ellen L.

AU - Olson, Janet E.

AU - Meijers-Heijboer, Hanne

AU - Van Den Ouweland, Ans

AU - Uitterlinden, André

AU - Rivadeneira, Fernando

AU - Milne, Roger L.

AU - Ribas, Gloria

AU - Gonzalez-Neira, Anna

AU - Benitez, Javier

AU - Hopper, John L.

AU - McCredie, Margaret

AU - Southey, Melissa

AU - Giles, Graham G.

AU - Schroen, Chris

AU - Justenhoven, Christina

AU - Brauch, Hiltrud

AU - Hamann, Ute

AU - Ko, Yon-Dschun

AU - Spurdle, Amanda B.

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - kConFab

AU - AOCS Management Group

AU - Mannermaa, Arto

AU - Kosma, Veli Matti

AU - Kataja, Vesa

AU - Hartikainen, Jaana

AU - Day, Nicholas E.

AU - Cox, David R.

AU - Ponder, Bruce A.J.

AU - Luccarini, Craig

AU - Conroy, Don

AU - Shah, Mitul

AU - Munday, Hannah

AU - Jordan, Clare

AU - Perkins, Barbara

AU - West, Judy

AU - Redman, Karen

AU - Driver, Kristy

AU - Aghmesheh, Morteza

AU - Amor, David

AU - Andrews, Lesley

AU - Antill, Yoland

AU - Armes, Jane

AU - Armitage, Shane

AU - Arnold, Leanne

AU - Balleine, Rosemary

AU - Begley, Glenn

AU - Beilby, John

AU - Bennett, Ian

AU - Bennett, Barbara

AU - Berry, Geoffrey

AU - Blackburn, Anneke

AU - Brennan, Meagan

AU - Brown, Melissa

AU - Buckley, Michael

AU - Burke, Jo

AU - Butow, Phyllis

AU - Byron, Keith

AU - Callen, David

AU - Campbell, Ian

AU - Clarke, Christine

AU - Colley, Alison

AU - Cotton, Dick

AU - Cui, Jisheng

AU - Culling, Bronwyn

AU - Cummings, Margaret

AU - Dawson, Sarah Jane

AU - Dixon, Joanne

AU - Dobrovic, Alexander

AU - Dudding, Tracy

AU - Edkins, Ted

AU - Eisenbruch, Maurice

AU - Farshid, Gelareh

AU - Fawcett, Susan

AU - Field, Michael

AU - Firgaira, Frank

AU - Fleming, Jean

AU - Forbes, John

AU - Friedlander, Michael

AU - Gaff, Clara

AU - Gardner, Mac

AU - Gattas, Mike

AU - George, Peter

AU - Gill, Grantley

AU - Goldblatt, Jack

AU - Greening, Sian

AU - Grist, Scott

AU - Haan, Eric

AU - Harris, Marion

AU - Hart, Stewart

AU - Hayward, Nick

AU - Hopper, John

AU - Humphrey, Evelyn

AU - Jenkins, Mark

AU - Jones, Alison

AU - Kefford, Rick

AU - Kirk, Judy

AU - Kollias, James

AU - Kovalenko, Sergey

AU - Lakhani, Sunil

AU - Leary, Jennifer

AU - Lim, Jacqueline

AU - Lindeman, Geoff

AU - Lipton, Lara

AU - Lobb, Liz

AU - Maclurcan, Mariette

AU - Mann, Graham

AU - Marsh, Deborah

AU - McKay, Michael

AU - Anne McLachlan, Sue

AU - Meiser, Bettina

AU - Milne, Roger

AU - Mitchell, Gillian

AU - Newman, Beth

AU - O'Loughlin, Imelda

AU - Osborne, Richard

AU - Peters, Lester

AU - Phillips, Kelly

AU - Price, Melanie

AU - Reeve, Jeanne

AU - Reeve, Tony

AU - Richards, Robert

AU - Rinehart, Gina

AU - Robinson, Bridget

AU - Rudzki, Barney

AU - Salisbury, Elizabeth

AU - Sambrook, Joe

AU - Saunders, Christobel

AU - Scott, Clare

AU - Scott, Elizabeth

AU - Scott, Rodney

AU - Seshadri, Ram

AU - Shelling, Andrew

AU - Spurdle, Amanda

AU - Suthers, Graeme

AU - Taylor, Donna

AU - Tennant, Christopher

AU - Thorne, Heather

AU - Townshend, Sharron

AU - Tucker, Kathy

AU - Tyler, Janet

AU - Venter, Deon

AU - Visvader, Jane

AU - Walpole, Ian

AU - Ward, Robin

AU - Waring, Paul

AU - Warner, Bev

AU - Warren, Graham

AU - Watson, Elizabeth

AU - Williams, Rachael

AU - Wilson, Judy

AU - Winship, Ingrid

AU - Young, Mary Ann

AU - Bowtell, David

AU - Green, Adele

AU - deFazio, Anna

AU - Gertig, Dorota

AU - Webb, Penny

PY - 2007/6/28

Y1 - 2007/6/28

N2 - 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 r2> 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.

AB - 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 r2> 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.

UR - http://www.scopus.com/inward/record.url?scp=34250006413&partnerID=8YFLogxK

U2 - 10.1038/nature05887

DO - 10.1038/nature05887

M3 - Article

C2 - 17529967

AN - SCOPUS:34250006413

SN - 0028-0836

VL - 447

SP - 1087

EP - 1093

JO - Nature

JF - Nature

ER -

Genome-wide association study identifies novel breast cancer susceptibility loci

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