Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype: Findings from the Breast Cancer Association Consortium

Jonine D. Figueroa, Montserrat Garcia-Closas, Manjeet Humphreys, Radka Platte, John L. Hopper, Melissa C. Southey, Carmel Apicella, Fleur Hammet, Marjanka K. Schmidt, Annegien Broeks, Rob A E M Tollenaar, Laura J. Van't Veer, Peter A. Fasching, Matthias W. Beckmann, Arif B. Ekici, Reiner Strick, Julian Peto, Isabel dos Santos Silva, Olivia Fletcher, Nichola JohnsonElinor Sawyer, Ian Tomlinson, Michael Kerin, Barbara Burwinkel, Federik Marme, Andreas Schneeweiss, Christof Sohn, Stig Bojesen, Henrik Flyger, Børge G. Nordestgaard, Javier Benítez, Roger L. Milne, Jose Ignacio Arias, M. Pilar Zamora, Hermann Brenner, Heiko Müller, Volker Arndt, Nazneen Rahman, Clare Turnbull, Sheila Seal, Anthony Renwick, Hiltrud Brauch, Christina Justenhoven, Thomas Brüning, Yon Dschun Ko, Christian Baisch, Hand Peter Fischer, Ute Hamann, Beate Pesch, Sylvia Rabstein, Volker Harth, Jenny Chang-Claude, Rebecca Hein, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia Bogdanova, Natalia Antonenkova, Yuri I. Rogov, Johann Hinrich Karstens, Marina Bermisheva, Darya Prokofieva, Shamil Hanafievich Gantcev, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Georgia Chenevix-Trench, Jonathan Beesley, Xiaoqing Chen, D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. M. Webb, Arto Mannermaa, Veli Matti Kosma, Ylermi Soini, Vesa Kataja, Diether Lambrechts, Betül T. Yesilyurt, Marie Rose Chrisiaens, Stephanie Peeters, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus Couch, Adam M. Lee, Robert Diasio, Xianshu Wang, Graham G. Giles, Gianluca Severi, Laura Baglietto, Catriona Maclean, Ken Offit, Mark Robson, Vijai Joseph, Mia Gaudet, Esther M. John, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene Andrulis, Julia A. Knight, Anna Marie Mulligan, Frances P. O'Malley, Louise A. Brinton, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Maartje Hooning, John W M Martens, Ans M W van den Ouweland, J. Margriet Collée, Per Hall, Kamila Czene, Angela Cox, Ian W. Brock, Malcolm W R Reed, Simon S. Cross, Paul Pharoah, Alison M. Dunning, Daehee Kang, Keun Young Yoo, Dong Young Noh, Sei Hyun Ahn, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen Yang Shen, Shian Ling Ding, Huan Ming Hsu, Jyh Cherng Yu, Hoda Anton-Culver, Argyrios Ziogas, Alan Ashworth, Anthony Swerdlow, Michael Jones, Nick Orr, Amy Trentham-Dietz, Kathleen Egan, Polly Newcomb, Linda Titus-Ernstoff, Doug Easton, Amanda B. Spurdle

Research output: Contribution to journalArticle

Abstract

A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.

Original languageEnglish (US)
Article numberddr368
Pages (from-to)4693-4706
Number of pages14
JournalHuman Molecular Genetics
Volume20
Issue number23
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Breast Neoplasms
Estrogen Receptors
Single Nucleotide Polymorphism
Neoplasms
Genome-Wide Association Study
Odds Ratio
Triple Negative Breast Neoplasms
Progesterone Receptors
Histology
Alleles
Pathology

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype : Findings from the Breast Cancer Association Consortium. / Figueroa, Jonine D.; Garcia-Closas, Montserrat; Humphreys, Manjeet; Platte, Radka; Hopper, John L.; Southey, Melissa C.; Apicella, Carmel; Hammet, Fleur; Schmidt, Marjanka K.; Broeks, Annegien; Tollenaar, Rob A E M; Van't Veer, Laura J.; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Strick, Reiner; Peto, Julian; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Federik; Schneeweiss, Andreas; Sohn, Christof; Bojesen, Stig; Flyger, Henrik; Nordestgaard, Børge G.; Benítez, Javier; Milne, Roger L.; Arias, Jose Ignacio; Zamora, M. Pilar; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Rahman, Nazneen; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Ko, Yon Dschun; Baisch, Christian; Fischer, Hand Peter; Hamann, Ute; Pesch, Beate; Rabstein, Sylvia; Harth, Volker; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuri I.; Karstens, Johann Hinrich; Bermisheva, Marina; Prokofieva, Darya; Gantcev, Shamil Hanafievich; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Bowtell, D.; Chenevix-Trench, G.; deFazio, A.; Gertig, D.; Green, A.; Webb, P. M.; Mannermaa, Arto; Kosma, Veli Matti; Soini, Ylermi; Kataja, Vesa; Lambrechts, Diether; Yesilyurt, Betül T.; Chrisiaens, Marie Rose; Peeters, Stephanie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus; Lee, Adam M.; Diasio, Robert; Wang, Xianshu; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Maclean, Catriona; Offit, Ken; Robson, Mark; Joseph, Vijai; Gaudet, Mia; John, Esther M.; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Brinton, Louise A.; Sherman, Mark E.; Lissowska, Jolanta; Chanock, Stephen J.; Hooning, Maartje; Martens, John W M; van den Ouweland, Ans M W; Collée, J. Margriet; Hall, Per; Czene, Kamila; Cox, Angela; Brock, Ian W.; Reed, Malcolm W R; Cross, Simon S.; Pharoah, Paul; Dunning, Alison M.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Ahn, Sei Hyun; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen Yang; Ding, Shian Ling; Hsu, Huan Ming; Yu, Jyh Cherng; Anton-Culver, Hoda; Ziogas, Argyrios; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Orr, Nick; Trentham-Dietz, Amy; Egan, Kathleen; Newcomb, Polly; Titus-Ernstoff, Linda; Easton, Doug; Spurdle, Amanda B.

In: Human Molecular Genetics, Vol. 20, No. 23, ddr368, 12.2011, p. 4693-4706.

Research output: Contribution to journalArticle

Figueroa, JD, Garcia-Closas, M, Humphreys, M, Platte, R, Hopper, JL, Southey, MC, Apicella, C, Hammet, F, Schmidt, MK, Broeks, A, Tollenaar, RAEM, Van't Veer, LJ, Fasching, PA, Beckmann, MW, Ekici, AB, Strick, R, Peto, J, Silva, IDS, Fletcher, O, Johnson, N, Sawyer, E, Tomlinson, I, Kerin, M, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Bojesen, S, Flyger, H, Nordestgaard, BG, Benítez, J, Milne, RL, Arias, JI, Zamora, MP, Brenner, H, Müller, H, Arndt, V, Rahman, N, Turnbull, C, Seal, S, Renwick, A, Brauch, H, Justenhoven, C, Brüning, T, Ko, YD, Baisch, C, Fischer, HP, Hamann, U, Pesch, B, Rabstein, S, Harth, V, Chang-Claude, J, Hein, R, Wang-Gohrke, S, Dörk, T, Schürmann, P, Bremer, M, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomäki, K, Blomqvist, C, Bogdanova, N, Antonenkova, N, Rogov, YI, Karstens, JH, Bermisheva, M, Prokofieva, D, Gantcev, SH, Khusnutdinova, E, Lindblom, A, Margolin, S, Chenevix-Trench, G, Beesley, J, Chen, X, Bowtell, D, Chenevix-Trench, G, deFazio, A, Gertig, D, Green, A, Webb, PM, Mannermaa, A, Kosma, VM, Soini, Y, Kataja, V, Lambrechts, D, Yesilyurt, BT, Chrisiaens, MR, Peeters, S, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, F, Lee, AM, Diasio, R, Wang, X, Giles, GG, Severi, G, Baglietto, L, Maclean, C, Offit, K, Robson, M, Joseph, V, Gaudet, M, John, EM, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, I, Knight, JA, Mulligan, AM, O'Malley, FP, Brinton, LA, Sherman, ME, Lissowska, J, Chanock, SJ, Hooning, M, Martens, JWM, van den Ouweland, AMW, Collée, JM, Hall, P, Czene, K, Cox, A, Brock, IW, Reed, MWR, Cross, SS, Pharoah, P, Dunning, AM, Kang, D, Yoo, KY, Noh, DY, Ahn, SH, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Shen, CY, Ding, SL, Hsu, HM, Yu, JC, Anton-Culver, H, Ziogas, A, Ashworth, A, Swerdlow, A, Jones, M, Orr, N, Trentham-Dietz, A, Egan, K, Newcomb, P, Titus-Ernstoff, L, Easton, D & Spurdle, AB 2011, 'Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype: Findings from the Breast Cancer Association Consortium', Human Molecular Genetics, vol. 20, no. 23, ddr368, pp. 4693-4706. https://doi.org/10.1093/hmg/ddr368
Figueroa, Jonine D. ; Garcia-Closas, Montserrat ; Humphreys, Manjeet ; Platte, Radka ; Hopper, John L. ; Southey, Melissa C. ; Apicella, Carmel ; Hammet, Fleur ; Schmidt, Marjanka K. ; Broeks, Annegien ; Tollenaar, Rob A E M ; Van't Veer, Laura J. ; Fasching, Peter A. ; Beckmann, Matthias W. ; Ekici, Arif B. ; Strick, Reiner ; Peto, Julian ; Silva, Isabel dos Santos ; Fletcher, Olivia ; Johnson, Nichola ; Sawyer, Elinor ; Tomlinson, Ian ; Kerin, Michael ; Burwinkel, Barbara ; Marme, Federik ; Schneeweiss, Andreas ; Sohn, Christof ; Bojesen, Stig ; Flyger, Henrik ; Nordestgaard, Børge G. ; Benítez, Javier ; Milne, Roger L. ; Arias, Jose Ignacio ; Zamora, M. Pilar ; Brenner, Hermann ; Müller, Heiko ; Arndt, Volker ; Rahman, Nazneen ; Turnbull, Clare ; Seal, Sheila ; Renwick, Anthony ; Brauch, Hiltrud ; Justenhoven, Christina ; Brüning, Thomas ; Ko, Yon Dschun ; Baisch, Christian ; Fischer, Hand Peter ; Hamann, Ute ; Pesch, Beate ; Rabstein, Sylvia ; Harth, Volker ; Chang-Claude, Jenny ; Hein, Rebecca ; Wang-Gohrke, Shan ; Dörk, Thilo ; Schürmann, Peter ; Bremer, Michael ; Hillemanns, Peter ; Nevanlinna, Heli ; Heikkinen, Tuomas ; Aittomäki, Kristiina ; Blomqvist, Carl ; Bogdanova, Natalia ; Antonenkova, Natalia ; Rogov, Yuri I. ; Karstens, Johann Hinrich ; Bermisheva, Marina ; Prokofieva, Darya ; Gantcev, Shamil Hanafievich ; Khusnutdinova, Elza ; Lindblom, Annika ; Margolin, Sara ; Chenevix-Trench, Georgia ; Beesley, Jonathan ; Chen, Xiaoqing ; Bowtell, D. ; Chenevix-Trench, G. ; deFazio, A. ; Gertig, D. ; Green, A. ; Webb, P. M. ; Mannermaa, Arto ; Kosma, Veli Matti ; Soini, Ylermi ; Kataja, Vesa ; Lambrechts, Diether ; Yesilyurt, Betül T. ; Chrisiaens, Marie Rose ; Peeters, Stephanie ; Radice, Paolo ; Peterlongo, Paolo ; Manoukian, Siranoush ; Barile, Monica ; Couch, Fergus ; Lee, Adam M. ; Diasio, Robert ; Wang, Xianshu ; Giles, Graham G. ; Severi, Gianluca ; Baglietto, Laura ; Maclean, Catriona ; Offit, Ken ; Robson, Mark ; Joseph, Vijai ; Gaudet, Mia ; John, Esther M. ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Andrulis, Irene ; Knight, Julia A. ; Mulligan, Anna Marie ; O'Malley, Frances P. ; Brinton, Louise A. ; Sherman, Mark E. ; Lissowska, Jolanta ; Chanock, Stephen J. ; Hooning, Maartje ; Martens, John W M ; van den Ouweland, Ans M W ; Collée, J. Margriet ; Hall, Per ; Czene, Kamila ; Cox, Angela ; Brock, Ian W. ; Reed, Malcolm W R ; Cross, Simon S. ; Pharoah, Paul ; Dunning, Alison M. ; Kang, Daehee ; Yoo, Keun Young ; Noh, Dong Young ; Ahn, Sei Hyun ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska, Katarzyna ; Durda, Katarzyna ; Sangrajrang, Suleeporn ; Gaborieau, Valerie ; Brennan, Paul ; McKay, James ; Shen, Chen Yang ; Ding, Shian Ling ; Hsu, Huan Ming ; Yu, Jyh Cherng ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Ashworth, Alan ; Swerdlow, Anthony ; Jones, Michael ; Orr, Nick ; Trentham-Dietz, Amy ; Egan, Kathleen ; Newcomb, Polly ; Titus-Ernstoff, Linda ; Easton, Doug ; Spurdle, Amanda B. / Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype : Findings from the Breast Cancer Association Consortium. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 23. pp. 4693-4706.
@article{2cf0e57d137b429d8f0cfc047ede40e0,
title = "Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype: Findings from the Breast Cancer Association Consortium",
abstract = "A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87{\%} had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95{\%} CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95{\%} CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.",
author = "Figueroa, {Jonine D.} and Montserrat Garcia-Closas and Manjeet Humphreys and Radka Platte and Hopper, {John L.} and Southey, {Melissa C.} and Carmel Apicella and Fleur Hammet and Schmidt, {Marjanka K.} and Annegien Broeks and Tollenaar, {Rob A E M} and {Van't Veer}, {Laura J.} and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Ekici, {Arif B.} and Reiner Strick and Julian Peto and Silva, {Isabel dos Santos} and Olivia Fletcher and Nichola Johnson and Elinor Sawyer and Ian Tomlinson and Michael Kerin and Barbara Burwinkel and Federik Marme and Andreas Schneeweiss and Christof Sohn and Stig Bojesen and Henrik Flyger and Nordestgaard, {B{\o}rge G.} and Javier Ben{\'i}tez and Milne, {Roger L.} and Arias, {Jose Ignacio} and Zamora, {M. Pilar} and Hermann Brenner and Heiko M{\"u}ller and Volker Arndt and Nazneen Rahman and Clare Turnbull and Sheila Seal and Anthony Renwick and Hiltrud Brauch and Christina Justenhoven and Thomas Br{\"u}ning and Ko, {Yon Dschun} and Christian Baisch and Fischer, {Hand Peter} and Ute Hamann and Beate Pesch and Sylvia Rabstein and Volker Harth and Jenny Chang-Claude and Rebecca Hein and Shan Wang-Gohrke and Thilo D{\"o}rk and Peter Sch{\"u}rmann and Michael Bremer and Peter Hillemanns and Heli Nevanlinna and Tuomas Heikkinen and Kristiina Aittom{\"a}ki and Carl Blomqvist and Natalia Bogdanova and Natalia Antonenkova and Rogov, {Yuri I.} and Karstens, {Johann Hinrich} and Marina Bermisheva and Darya Prokofieva and Gantcev, {Shamil Hanafievich} and Elza Khusnutdinova and Annika Lindblom and Sara Margolin and Georgia Chenevix-Trench and Jonathan Beesley and Xiaoqing Chen and D. Bowtell and G. Chenevix-Trench and A. deFazio and D. Gertig and A. Green and Webb, {P. M.} and Arto Mannermaa and Kosma, {Veli Matti} and Ylermi Soini and Vesa Kataja and Diether Lambrechts and Yesilyurt, {Bet{\"u}l T.} and Chrisiaens, {Marie Rose} and Stephanie Peeters and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Monica Barile and Fergus Couch and Lee, {Adam M.} and Robert Diasio and Xianshu Wang and Giles, {Graham G.} and Gianluca Severi and Laura Baglietto and Catriona Maclean and Ken Offit and Mark Robson and Vijai Joseph and Mia Gaudet and John, {Esther M.} and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Irene Andrulis and Knight, {Julia A.} and Mulligan, {Anna Marie} and O'Malley, {Frances P.} and Brinton, {Louise A.} and Sherman, {Mark E.} and Jolanta Lissowska and Chanock, {Stephen J.} and Maartje Hooning and Martens, {John W M} and {van den Ouweland}, {Ans M W} and Coll{\'e}e, {J. Margriet} and Per Hall and Kamila Czene and Angela Cox and Brock, {Ian W.} and Reed, {Malcolm W R} and Cross, {Simon S.} and Paul Pharoah and Dunning, {Alison M.} and Daehee Kang and Yoo, {Keun Young} and Noh, {Dong Young} and Ahn, {Sei Hyun} and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James McKay and Shen, {Chen Yang} and Ding, {Shian Ling} and Hsu, {Huan Ming} and Yu, {Jyh Cherng} and Hoda Anton-Culver and Argyrios Ziogas and Alan Ashworth and Anthony Swerdlow and Michael Jones and Nick Orr and Amy Trentham-Dietz and Kathleen Egan and Polly Newcomb and Linda Titus-Ernstoff and Doug Easton and Spurdle, {Amanda B.}",
year = "2011",
month = "12",
doi = "10.1093/hmg/ddr368",
language = "English (US)",
volume = "20",
pages = "4693--4706",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "23",

}

TY - JOUR

T1 - Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype

T2 - Findings from the Breast Cancer Association Consortium

AU - Figueroa, Jonine D.

AU - Garcia-Closas, Montserrat

AU - Humphreys, Manjeet

AU - Platte, Radka

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Apicella, Carmel

AU - Hammet, Fleur

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Tollenaar, Rob A E M

AU - Van't Veer, Laura J.

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Ekici, Arif B.

AU - Strick, Reiner

AU - Peto, Julian

AU - Silva, Isabel dos Santos

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael

AU - Burwinkel, Barbara

AU - Marme, Federik

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Bojesen, Stig

AU - Flyger, Henrik

AU - Nordestgaard, Børge G.

AU - Benítez, Javier

AU - Milne, Roger L.

AU - Arias, Jose Ignacio

AU - Zamora, M. Pilar

AU - Brenner, Hermann

AU - Müller, Heiko

AU - Arndt, Volker

AU - Rahman, Nazneen

AU - Turnbull, Clare

AU - Seal, Sheila

AU - Renwick, Anthony

AU - Brauch, Hiltrud

AU - Justenhoven, Christina

AU - Brüning, Thomas

AU - Ko, Yon Dschun

AU - Baisch, Christian

AU - Fischer, Hand Peter

AU - Hamann, Ute

AU - Pesch, Beate

AU - Rabstein, Sylvia

AU - Harth, Volker

AU - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Wang-Gohrke, Shan

AU - Dörk, Thilo

AU - Schürmann, Peter

AU - Bremer, Michael

AU - Hillemanns, Peter

AU - Nevanlinna, Heli

AU - Heikkinen, Tuomas

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Bogdanova, Natalia

AU - Antonenkova, Natalia

AU - Rogov, Yuri I.

AU - Karstens, Johann Hinrich

AU - Bermisheva, Marina

AU - Prokofieva, Darya

AU - Gantcev, Shamil Hanafievich

AU - Khusnutdinova, Elza

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Bowtell, D.

AU - Chenevix-Trench, G.

AU - deFazio, A.

AU - Gertig, D.

AU - Green, A.

AU - Webb, P. M.

AU - Mannermaa, Arto

AU - Kosma, Veli Matti

AU - Soini, Ylermi

AU - Kataja, Vesa

AU - Lambrechts, Diether

AU - Yesilyurt, Betül T.

AU - Chrisiaens, Marie Rose

AU - Peeters, Stephanie

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Barile, Monica

AU - Couch, Fergus

AU - Lee, Adam M.

AU - Diasio, Robert

AU - Wang, Xianshu

AU - Giles, Graham G.

AU - Severi, Gianluca

AU - Baglietto, Laura

AU - Maclean, Catriona

AU - Offit, Ken

AU - Robson, Mark

AU - Joseph, Vijai

AU - Gaudet, Mia

AU - John, Esther M.

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Andrulis, Irene

AU - Knight, Julia A.

AU - Mulligan, Anna Marie

AU - O'Malley, Frances P.

AU - Brinton, Louise A.

AU - Sherman, Mark E.

AU - Lissowska, Jolanta

AU - Chanock, Stephen J.

AU - Hooning, Maartje

AU - Martens, John W M

AU - van den Ouweland, Ans M W

AU - Collée, J. Margriet

AU - Hall, Per

AU - Czene, Kamila

AU - Cox, Angela

AU - Brock, Ian W.

AU - Reed, Malcolm W R

AU - Cross, Simon S.

AU - Pharoah, Paul

AU - Dunning, Alison M.

AU - Kang, Daehee

AU - Yoo, Keun Young

AU - Noh, Dong Young

AU - Ahn, Sei Hyun

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Brennan, Paul

AU - McKay, James

AU - Shen, Chen Yang

AU - Ding, Shian Ling

AU - Hsu, Huan Ming

AU - Yu, Jyh Cherng

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Ashworth, Alan

AU - Swerdlow, Anthony

AU - Jones, Michael

AU - Orr, Nick

AU - Trentham-Dietz, Amy

AU - Egan, Kathleen

AU - Newcomb, Polly

AU - Titus-Ernstoff, Linda

AU - Easton, Doug

AU - Spurdle, Amanda B.

PY - 2011/12

Y1 - 2011/12

N2 - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.

AB - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.

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UR - http://www.scopus.com/inward/citedby.url?scp=81255209196&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr368

DO - 10.1093/hmg/ddr368

M3 - Article

C2 - 21852249

AN - SCOPUS:81255209196

VL - 20

SP - 4693

EP - 4706

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 23

M1 - ddr368

ER -