Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer

Roger L. Milne, Ellen L. Goode, Montserrat García-Closas, Fergus J. Couch, Gianluca Severi, Rebecca Hein, Zachary Fredericksen, Núria Malats, M. Pilar Zamora, Jose Ignacio Arias Pérez, Javier Benítez, Thilo Dörk, Peter Schürmann, Johann H. Karstens, Peter Hillemanns, Angela Cox, Ian W. Brock, Graeme Elliot, Simon S. Cross, Sheila Seal & 123 others Clare Turnbull, Anthony Renwick, Nazneen Rahman, Chen Yang Shen, Jyh Cherng Yu, Chiun Sheng Huang, Ming Feng Hou, Børge G. Nordestgaard, Stig E. Bojesen, Charlotte Lanng, Grethe Grenaker Alnæs, Vessela Kristensen, Anne Lise Børrensen-Dale, John L. Hopper, Gillian S. Dite, Carmel Apicella, Melissa C. Southey, Diether Lambrechts, Betül T. Yesilyurt, Giuseppe Floris, Karin Leunen, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Jenny Chang-Claude, Shan Wang-Gohrke, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Graham G. Giles, Laura Baglietto, Esther M. John, Alexander Miron, Stephen J. Chanock, Jolanta Lissowska, Mark E. Sherman, Jonine D. Figueroa, Natalia V. Bogdanova, Natalia N. Antonenkova, Iosif V. Zalutsky, Yuri I. Rogov, Peter A. Fasching, Christian M. Bayer, Arif B. Ekici, Matthias W. Beckmann, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Alfons Meindl, Joerg Heil, Claus R. Bartram, Rita K. Schmutzler, Gilles D. Thomas, Robert N. Hoover, Olivia Fletcher, Lorna J. Gibson, Isabel Dos Santos Silva, Julian Peto, Stefan Nickels, Dieter Flesch-Janys, Hoda Anton-Culver, Argyrios Ziogas, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Marjanka K. Schmidt, Annegien Broeks, Laura J. Van't Veer, Rob A E M Tollenaar, Paul D P Pharoah, Alison M. Dunning, Karen A. Pooley, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Daehee Kang, Keun Young Yoo, Dong Young Noh, Sei Hyun Ahn, David J. Hunter, Susan E. Hankinson, Peter Kraft, Sara Lindstrom, Xiaoqing Chen, Jonathan Beesley, Ute Hamann, Volker Harth, Christina Justenhoven, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Maartje Hooning, Antoinette Hollestelle, Rogier A. Oldenburg, Madeleine Tilanus-Linthorst, Elza Khusnutdinova, Marina Bermisheva, Darya Prokofieva, Albina Farahtdinova, Janet E. Olson, Xianshu Wang, Manjeet K. Humphreys, Qin Wang, Georgia Chenevix-Trench, Douglas F. Easton

Research output: Contribution to journalArticle

Abstract

Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10 -18) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)- positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10 -18 vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P heterogeneity = 2 × 10 -7); heterogeneity by ER status was not observed (P= 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10 -7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.

Original languageEnglish (US)
Pages (from-to)2222-2231
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume20
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

Progesterone Receptors
Breast Neoplasms
Carcinoma, Intraductal, Noninfiltrating
Alleles
Estrogen Receptors
Neoplasms
Single Nucleotide Polymorphism
Logistic Models

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Milne, R. L., Goode, E. L., García-Closas, M., Couch, F. J., Severi, G., Hein, R., ... Easton, D. F. (2011). Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer. Cancer Epidemiology Biomarkers and Prevention, 20(10), 2222-2231. https://doi.org/10.1158/1055-9965.EPI-11-0569

Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer. / Milne, Roger L.; Goode, Ellen L.; García-Closas, Montserrat; Couch, Fergus J.; Severi, Gianluca; Hein, Rebecca; Fredericksen, Zachary; Malats, Núria; Zamora, M. Pilar; Pérez, Jose Ignacio Arias; Benítez, Javier; Dörk, Thilo; Schürmann, Peter; Karstens, Johann H.; Hillemanns, Peter; Cox, Angela; Brock, Ian W.; Elliot, Graeme; Cross, Simon S.; Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Rahman, Nazneen; Shen, Chen Yang; Yu, Jyh Cherng; Huang, Chiun Sheng; Hou, Ming Feng; Nordestgaard, Børge G.; Bojesen, Stig E.; Lanng, Charlotte; Alnæs, Grethe Grenaker; Kristensen, Vessela; Børrensen-Dale, Anne Lise; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Lambrechts, Diether; Yesilyurt, Betül T.; Floris, Giuseppe; Leunen, Karin; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Chang-Claude, Jenny; Wang-Gohrke, Shan; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Giles, Graham G.; Baglietto, Laura; John, Esther M.; Miron, Alexander; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Figueroa, Jonine D.; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Zalutsky, Iosif V.; Rogov, Yuri I.; Fasching, Peter A.; Bayer, Christian M.; Ekici, Arif B.; Beckmann, Matthias W.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Meindl, Alfons; Heil, Joerg; Bartram, Claus R.; Schmutzler, Rita K.; Thomas, Gilles D.; Hoover, Robert N.; Fletcher, Olivia; Gibson, Lorna J.; Dos Santos Silva, Isabel; Peto, Julian; Nickels, Stefan; Flesch-Janys, Dieter; Anton-Culver, Hoda; Ziogas, Argyrios; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Tollenaar, Rob A E M; Pharoah, Paul D P; Dunning, Alison M.; Pooley, Karen A.; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Ahn, Sei Hyun; Hunter, David J.; Hankinson, Susan E.; Kraft, Peter; Lindstrom, Sara; Chen, Xiaoqing; Beesley, Jonathan; Hamann, Ute; Harth, Volker; Justenhoven, Christina; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje; Hollestelle, Antoinette; Oldenburg, Rogier A.; Tilanus-Linthorst, Madeleine; Khusnutdinova, Elza; Bermisheva, Marina; Prokofieva, Darya; Farahtdinova, Albina; Olson, Janet E.; Wang, Xianshu; Humphreys, Manjeet K.; Wang, Qin; Chenevix-Trench, Georgia; Easton, Douglas F.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 20, No. 10, 10.2011, p. 2222-2231.

Research output: Contribution to journalArticle

Milne, RL, Goode, EL, García-Closas, M, Couch, FJ, Severi, G, Hein, R, Fredericksen, Z, Malats, N, Zamora, MP, Pérez, JIA, Benítez, J, Dörk, T, Schürmann, P, Karstens, JH, Hillemanns, P, Cox, A, Brock, IW, Elliot, G, Cross, SS, Seal, S, Turnbull, C, Renwick, A, Rahman, N, Shen, CY, Yu, JC, Huang, CS, Hou, MF, Nordestgaard, BG, Bojesen, SE, Lanng, C, Alnæs, GG, Kristensen, V, Børrensen-Dale, AL, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Chang-Claude, J, Wang-Gohrke, S, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Giles, GG, Baglietto, L, John, EM, Miron, A, Chanock, SJ, Lissowska, J, Sherman, ME, Figueroa, JD, Bogdanova, NV, Antonenkova, NN, Zalutsky, IV, Rogov, YI, Fasching, PA, Bayer, CM, Ekici, AB, Beckmann, MW, Brenner, H, Müller, H, Arndt, V, Stegmaier, C, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Meindl, A, Heil, J, Bartram, CR, Schmutzler, RK, Thomas, GD, Hoover, RN, Fletcher, O, Gibson, LJ, Dos Santos Silva, I, Peto, J, Nickels, S, Flesch-Janys, D, Anton-Culver, H, Ziogas, A, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Schmidt, MK, Broeks, A, Van't Veer, LJ, Tollenaar, RAEM, Pharoah, PDP, Dunning, AM, Pooley, KA, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Kang, D, Yoo, KY, Noh, DY, Ahn, SH, Hunter, DJ, Hankinson, SE, Kraft, P, Lindstrom, S, Chen, X, Beesley, J, Hamann, U, Harth, V, Justenhoven, C, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Hooning, M, Hollestelle, A, Oldenburg, RA, Tilanus-Linthorst, M, Khusnutdinova, E, Bermisheva, M, Prokofieva, D, Farahtdinova, A, Olson, JE, Wang, X, Humphreys, MK, Wang, Q, Chenevix-Trench, G & Easton, DF 2011, 'Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 10, pp. 2222-2231. https://doi.org/10.1158/1055-9965.EPI-11-0569
Milne, Roger L. ; Goode, Ellen L. ; García-Closas, Montserrat ; Couch, Fergus J. ; Severi, Gianluca ; Hein, Rebecca ; Fredericksen, Zachary ; Malats, Núria ; Zamora, M. Pilar ; Pérez, Jose Ignacio Arias ; Benítez, Javier ; Dörk, Thilo ; Schürmann, Peter ; Karstens, Johann H. ; Hillemanns, Peter ; Cox, Angela ; Brock, Ian W. ; Elliot, Graeme ; Cross, Simon S. ; Seal, Sheila ; Turnbull, Clare ; Renwick, Anthony ; Rahman, Nazneen ; Shen, Chen Yang ; Yu, Jyh Cherng ; Huang, Chiun Sheng ; Hou, Ming Feng ; Nordestgaard, Børge G. ; Bojesen, Stig E. ; Lanng, Charlotte ; Alnæs, Grethe Grenaker ; Kristensen, Vessela ; Børrensen-Dale, Anne Lise ; Hopper, John L. ; Dite, Gillian S. ; Apicella, Carmel ; Southey, Melissa C. ; Lambrechts, Diether ; Yesilyurt, Betül T. ; Floris, Giuseppe ; Leunen, Karin ; Sangrajrang, Suleeporn ; Gaborieau, Valerie ; Brennan, Paul ; McKay, James ; Chang-Claude, Jenny ; Wang-Gohrke, Shan ; Radice, Paolo ; Peterlongo, Paolo ; Manoukian, Siranoush ; Barile, Monica ; Giles, Graham G. ; Baglietto, Laura ; John, Esther M. ; Miron, Alexander ; Chanock, Stephen J. ; Lissowska, Jolanta ; Sherman, Mark E. ; Figueroa, Jonine D. ; Bogdanova, Natalia V. ; Antonenkova, Natalia N. ; Zalutsky, Iosif V. ; Rogov, Yuri I. ; Fasching, Peter A. ; Bayer, Christian M. ; Ekici, Arif B. ; Beckmann, Matthias W. ; Brenner, Hermann ; Müller, Heiko ; Arndt, Volker ; Stegmaier, Christa ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Mulligan, Anna Marie ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli Matti ; Hartikainen, Jaana M. ; Meindl, Alfons ; Heil, Joerg ; Bartram, Claus R. ; Schmutzler, Rita K. ; Thomas, Gilles D. ; Hoover, Robert N. ; Fletcher, Olivia ; Gibson, Lorna J. ; Dos Santos Silva, Isabel ; Peto, Julian ; Nickels, Stefan ; Flesch-Janys, Dieter ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Sawyer, Elinor ; Tomlinson, Ian ; Kerin, Michael ; Miller, Nicola ; Schmidt, Marjanka K. ; Broeks, Annegien ; Van't Veer, Laura J. ; Tollenaar, Rob A E M ; Pharoah, Paul D P ; Dunning, Alison M. ; Pooley, Karen A. ; Marme, Frederik ; Schneeweiss, Andreas ; Sohn, Christof ; Burwinkel, Barbara ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska, Katarzyna ; Durda, Katarzyna ; Kang, Daehee ; Yoo, Keun Young ; Noh, Dong Young ; Ahn, Sei Hyun ; Hunter, David J. ; Hankinson, Susan E. ; Kraft, Peter ; Lindstrom, Sara ; Chen, Xiaoqing ; Beesley, Jonathan ; Hamann, Ute ; Harth, Volker ; Justenhoven, Christina ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Hooning, Maartje ; Hollestelle, Antoinette ; Oldenburg, Rogier A. ; Tilanus-Linthorst, Madeleine ; Khusnutdinova, Elza ; Bermisheva, Marina ; Prokofieva, Darya ; Farahtdinova, Albina ; Olson, Janet E. ; Wang, Xianshu ; Humphreys, Manjeet K. ; Wang, Qin ; Chenevix-Trench, Georgia ; Easton, Douglas F. / Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2011 ; Vol. 20, No. 10. pp. 2222-2231.
@article{5e037a4a07674b849f55d7b523f79cd3,
title = "Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer",
abstract = "Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95{\%} CI = 1.08-1.14, P = 7 × 10 -18) for invasive breast cancer and 1.10 (95{\%} CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95{\%}CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)- positive disease (per-allele OR = 1.16, 95{\%} CI = 1.12-1.20, P = 1 × 10 -18 vs. OR = 1.03, 95{\%} CI = 0.99-1.07, P = 0.2 for PR-negative disease; P heterogeneity = 2 × 10 -7); heterogeneity by ER status was not observed (P= 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95{\%} CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10 -7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.",
author = "Milne, {Roger L.} and Goode, {Ellen L.} and Montserrat Garc{\'i}a-Closas and Couch, {Fergus J.} and Gianluca Severi and Rebecca Hein and Zachary Fredericksen and N{\'u}ria Malats and Zamora, {M. Pilar} and P{\'e}rez, {Jose Ignacio Arias} and Javier Ben{\'i}tez and Thilo D{\"o}rk and Peter Sch{\"u}rmann and Karstens, {Johann H.} and Peter Hillemanns and Angela Cox and Brock, {Ian W.} and Graeme Elliot and Cross, {Simon S.} and Sheila Seal and Clare Turnbull and Anthony Renwick and Nazneen Rahman and Shen, {Chen Yang} and Yu, {Jyh Cherng} and Huang, {Chiun Sheng} and Hou, {Ming Feng} and Nordestgaard, {B{\o}rge G.} and Bojesen, {Stig E.} and Charlotte Lanng and Aln{\ae}s, {Grethe Grenaker} and Vessela Kristensen and B{\o}rrensen-Dale, {Anne Lise} and Hopper, {John L.} and Dite, {Gillian S.} and Carmel Apicella and Southey, {Melissa C.} and Diether Lambrechts and Yesilyurt, {Bet{\"u}l T.} and Giuseppe Floris and Karin Leunen and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James McKay and Jenny Chang-Claude and Shan Wang-Gohrke and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Monica Barile and Giles, {Graham G.} and Laura Baglietto and John, {Esther M.} and Alexander Miron and Chanock, {Stephen J.} and Jolanta Lissowska and Sherman, {Mark E.} and Figueroa, {Jonine D.} and Bogdanova, {Natalia V.} and Antonenkova, {Natalia N.} and Zalutsky, {Iosif V.} and Rogov, {Yuri I.} and Fasching, {Peter A.} and Bayer, {Christian M.} and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Hermann Brenner and Heiko M{\"u}ller and Volker Arndt and Christa Stegmaier and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Mulligan, {Anna Marie} and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Alfons Meindl and Joerg Heil and Bartram, {Claus R.} and Schmutzler, {Rita K.} and Thomas, {Gilles D.} and Hoover, {Robert N.} and Olivia Fletcher and Gibson, {Lorna J.} and {Dos Santos Silva}, Isabel and Julian Peto and Stefan Nickels and Dieter Flesch-Janys and Hoda Anton-Culver and Argyrios Ziogas and Elinor Sawyer and Ian Tomlinson and Michael Kerin and Nicola Miller and Schmidt, {Marjanka K.} and Annegien Broeks and {Van't Veer}, {Laura J.} and Tollenaar, {Rob A E M} and Pharoah, {Paul D P} and Dunning, {Alison M.} and Pooley, {Karen A.} and Frederik Marme and Andreas Schneeweiss and Christof Sohn and Barbara Burwinkel and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Daehee Kang and Yoo, {Keun Young} and Noh, {Dong Young} and Ahn, {Sei Hyun} and Hunter, {David J.} and Hankinson, {Susan E.} and Peter Kraft and Sara Lindstrom and Xiaoqing Chen and Jonathan Beesley and Ute Hamann and Volker Harth and Christina Justenhoven and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Maartje Hooning and Antoinette Hollestelle and Oldenburg, {Rogier A.} and Madeleine Tilanus-Linthorst and Elza Khusnutdinova and Marina Bermisheva and Darya Prokofieva and Albina Farahtdinova and Olson, {Janet E.} and Xianshu Wang and Humphreys, {Manjeet K.} and Qin Wang and Georgia Chenevix-Trench and Easton, {Douglas F.}",
year = "2011",
month = "10",
doi = "10.1158/1055-9965.EPI-11-0569",
language = "English (US)",
volume = "20",
pages = "2222--2231",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer

AU - Milne, Roger L.

AU - Goode, Ellen L.

AU - García-Closas, Montserrat

AU - Couch, Fergus J.

AU - Severi, Gianluca

AU - Hein, Rebecca

AU - Fredericksen, Zachary

AU - Malats, Núria

AU - Zamora, M. Pilar

AU - Pérez, Jose Ignacio Arias

AU - Benítez, Javier

AU - Dörk, Thilo

AU - Schürmann, Peter

AU - Karstens, Johann H.

AU - Hillemanns, Peter

AU - Cox, Angela

AU - Brock, Ian W.

AU - Elliot, Graeme

AU - Cross, Simon S.

AU - Seal, Sheila

AU - Turnbull, Clare

AU - Renwick, Anthony

AU - Rahman, Nazneen

AU - Shen, Chen Yang

AU - Yu, Jyh Cherng

AU - Huang, Chiun Sheng

AU - Hou, Ming Feng

AU - Nordestgaard, Børge G.

AU - Bojesen, Stig E.

AU - Lanng, Charlotte

AU - Alnæs, Grethe Grenaker

AU - Kristensen, Vessela

AU - Børrensen-Dale, Anne Lise

AU - Hopper, John L.

AU - Dite, Gillian S.

AU - Apicella, Carmel

AU - Southey, Melissa C.

AU - Lambrechts, Diether

AU - Yesilyurt, Betül T.

AU - Floris, Giuseppe

AU - Leunen, Karin

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Brennan, Paul

AU - McKay, James

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Barile, Monica

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - John, Esther M.

AU - Miron, Alexander

AU - Chanock, Stephen J.

AU - Lissowska, Jolanta

AU - Sherman, Mark E.

AU - Figueroa, Jonine D.

AU - Bogdanova, Natalia V.

AU - Antonenkova, Natalia N.

AU - Zalutsky, Iosif V.

AU - Rogov, Yuri I.

AU - Fasching, Peter A.

AU - Bayer, Christian M.

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Brenner, Hermann

AU - Müller, Heiko

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Meindl, Alfons

AU - Heil, Joerg

AU - Bartram, Claus R.

AU - Schmutzler, Rita K.

AU - Thomas, Gilles D.

AU - Hoover, Robert N.

AU - Fletcher, Olivia

AU - Gibson, Lorna J.

AU - Dos Santos Silva, Isabel

AU - Peto, Julian

AU - Nickels, Stefan

AU - Flesch-Janys, Dieter

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael

AU - Miller, Nicola

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Van't Veer, Laura J.

AU - Tollenaar, Rob A E M

AU - Pharoah, Paul D P

AU - Dunning, Alison M.

AU - Pooley, Karen A.

AU - Marme, Frederik

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Burwinkel, Barbara

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Kang, Daehee

AU - Yoo, Keun Young

AU - Noh, Dong Young

AU - Ahn, Sei Hyun

AU - Hunter, David J.

AU - Hankinson, Susan E.

AU - Kraft, Peter

AU - Lindstrom, Sara

AU - Chen, Xiaoqing

AU - Beesley, Jonathan

AU - Hamann, Ute

AU - Harth, Volker

AU - Justenhoven, Christina

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Hooning, Maartje

AU - Hollestelle, Antoinette

AU - Oldenburg, Rogier A.

AU - Tilanus-Linthorst, Madeleine

AU - Khusnutdinova, Elza

AU - Bermisheva, Marina

AU - Prokofieva, Darya

AU - Farahtdinova, Albina

AU - Olson, Janet E.

AU - Wang, Xianshu

AU - Humphreys, Manjeet K.

AU - Wang, Qin

AU - Chenevix-Trench, Georgia

AU - Easton, Douglas F.

PY - 2011/10

Y1 - 2011/10

N2 - Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10 -18) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)- positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10 -18 vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P heterogeneity = 2 × 10 -7); heterogeneity by ER status was not observed (P= 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10 -7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.

AB - Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10 -18) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)- positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10 -18 vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P heterogeneity = 2 × 10 -7); heterogeneity by ER status was not observed (P= 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10 -7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.

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U2 - 10.1158/1055-9965.EPI-11-0569

DO - 10.1158/1055-9965.EPI-11-0569

M3 - Article

VL - 20

SP - 2222

EP - 2231

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 10

ER -