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 Johnson; Elinor 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; Jenny Chang-Claude; Rebecca Hein; Shan Wang-Gohrke; Thilo Dörk; Peter Schürmann; Michael Bremer; GENICA Network

doi:http://dx.doi.org/10.1093/hmg/ddr368

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, Jenny Chang-Claude, Rebecca Hein, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Michael Bremer, GENICA Network

60 Citations (Scopus)

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 (r²=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 language	English
Journal	Human Molecular Genetics
Volume	20
Issue number	23
Pages (from-to)	4693-706
Number of pages	14
ISSN	0964-6906
DOIs	https://doi.org/10.1093/hmg/ddr368
Publication status	Published - 1 Dec 2011

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Figueroa, J. D., Garcia-Closas, M., Humphreys, M., Platte, R., Hopper, J. L., Southey, M. C., Apicella, C., Hammet, F., Schmidt, M. K., Broeks, A., Tollenaar, R. A. E. M., Van't Veer, L. J., Fasching, P. A., Beckmann, M. W., Ekici, A. B., Strick, R., Peto, J., dos Santos Silva, I., Fletcher, O., ... GENICA Network (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, 20(23), 4693-706. https://doi.org/10.1093/hmg/ddr368

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 et al.

In: Human Molecular Genetics, Vol. 20, No. 23, 01.12.2011, p. 4693-706.

Research output: Contribution to journal › Journal article › Research › peer-review

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, dos Santos Silva, I, 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, Ignacio Arias, J, Zamora, MP, Brenner, H, Müller, H, Arndt, V, Rahman, N, Turnbull, C, Seal, S, Renwick, A, Brauch, H, Justenhoven, C, Brüning, T, Chang-Claude, J, Hein, R, Wang-Gohrke, S, Dörk, T, Schürmann, P, Bremer, M & GENICA Network 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, pp. 4693-706. https://doi.org/10.1093/hmg/ddr368

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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 (r2=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 {dos Santos Silva}, Isabel 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 {Ignacio Arias}, Jose 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 Jenny Chang-Claude and Rebecca Hein and Shan Wang-Gohrke and Thilo D{\"o}rk and Peter Sch{\"u}rmann and Michael Bremer and B{\o}rge Nordestgaard",

year = "2011",

month = dec,

day = "1",

doi = "http://dx.doi.org/10.1093/hmg/ddr368",

language = "English",

volume = "20",

pages = "4693--706",

journal = "Human Molecular Genetics",

issn = "0964-6906",

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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 - dos Santos Silva, Isabel

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 - Ignacio Arias, Jose

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 - Chang-Claude, Jenny

AU - Hein, Rebecca

AU - Wang-Gohrke, Shan

AU - Dörk, Thilo

AU - Schürmann, Peter

AU - Bremer, Michael

AU - GENICA Network

PY - 2011/12/1

Y1 - 2011/12/1

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 (r2=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 (r2=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.

U2 - http://dx.doi.org/10.1093/hmg/ddr368

DO - http://dx.doi.org/10.1093/hmg/ddr368

M3 - Journal article

SN - 0964-6906

VL - 20

SP - 4693

EP - 4706

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 23

ER -

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

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