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1. Correction: Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

Author: Rebecca Hein, Melanie Maranian, John L. Hopper, Miroslaw K. Kapuscinski, Melissa C. Southey, Daniel J. Park, Marjanka K. Schmidt, Annegien Broeks, Frans B. L. Hogervorst, H. Bas Bueno-de-Mesquit, Kenneth R. Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Puttisak Puttawibul, Peter A. Fasching, Alexander Hein, Arif B. Ekici, Matthias W. Beckmann, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Frederick Marmee, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Stig E. Bojesen, Børge G. Nordestgaard, Henrik Flyger, Roger L. Milne, Jose Ignacio Arias Perez, M. Pilar Zamora, Javier Benítez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A. Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Nazneen Rahman, Sheila Seal, Clare Turnbull, Anthony Renwick, Alfons Meindl, Sarah Schott, Claus R. Bartram, Rita K. Schmutzler, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Johann H. Karstens, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia V. Bogdanova, Iosif V. Zalutsky, Natalia N. Antonenkova, Marina Bermisheva, Darya Prokovieva, Albina Farahtdinova, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana Hartikainen, Xiaoqing Chen, Jonathan Beesley, kConFab Investigators, Diether Lambrechts, Hui Zhao, Patrick Neven, Hans Wildiers, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Graham G. Giles, Laura Baglietto, Catriona A. McLean, Gianluca Severi, Kenneth Offit, Mark Robson, Mia M. Gaudet, Joseph Vijai, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børresen-Dale, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Jonine D. Figueroa, Montserrat García-Closas, Jolanta Lissowska, Mark E. Sherman, Maartje Hooning, John W. M. Martens, Caroline Seynaeve, Margriet Collée, Per Hall, Keith Humpreys, Kamila Czene, Jianjun Liu, Angela Cox, Ian W. Brock, Simon S. Cross, Malcolm W. R. Reed, Shahana Ahmed, Maya Ghoussaini, Paul DP. Pharoah, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen-Yang Shen, Jyh-Cherng Yu, Huan-Ming Hsu, Ming-Feng Hou, Nick Orr, Minouk Schoemaker, Alan Ashworth, Anthony Swerdlow, Amy Trentham-Dietz, Polly A. Newcomb, Linda Titus, Kathleen M. Egan, Georgia Chenevix-Trench, Antonis C. Antoniou, Manjeet K. Humphreys, Jonathan Morrison, Jenny Chang-Claude, Douglas F. Easton, and Alison M. Dunning
Subjects: Medicine, Science
Published: 2012
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2. Supplementary Tables 1 and 2; legend for Supplementary Table 3 from TGF-β Signaling Pathway and Breast Cancer Susceptibility

Author: Alison M. Dunning, James C. Metcalfe, Robin Hesketh, Douglas F. Easton, Paul D. Pharoah, Jolanta Lissowska, Jonine Figueroa, Montserrat Garcia-Closas, Manjeet K. Humphreys, Kristy Driver, Caroline Baynes, Craig Luccarini, and Serena Scollen
Abstract: Supplementary Tables 1 and 2; legend for Supplementary Table 3 from TGF-β Signaling Pathway and Breast Cancer Susceptibility
Published: 2023
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3. Supplementary Table 4 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 70K
Published: 2023
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4. Supplementary Table 3 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 71K
Published: 2023
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5. Supplementary Table 2 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 94K
Published: 2023
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6. Data from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
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; Pheterogeneity = 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. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.
Published: 2023
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7. Supplementary Table 3 from TGF-β Signaling Pathway and Breast Cancer Susceptibility

Author: Alison M. Dunning, James C. Metcalfe, Robin Hesketh, Douglas F. Easton, Paul D. Pharoah, Jolanta Lissowska, Jonine Figueroa, Montserrat Garcia-Closas, Manjeet K. Humphreys, Kristy Driver, Caroline Baynes, Craig Luccarini, and Serena Scollen
Abstract: Supplementary Table 3 from TGF-β Signaling Pathway and Breast Cancer Susceptibility
Published: 2023
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8. Data from TGF-β Signaling Pathway and Breast Cancer Susceptibility

Author: Alison M. Dunning, James C. Metcalfe, Robin Hesketh, Douglas F. Easton, Paul D. Pharoah, Jolanta Lissowska, Jonine Figueroa, Montserrat Garcia-Closas, Manjeet K. Humphreys, Kristy Driver, Caroline Baynes, Craig Luccarini, and Serena Scollen
Abstract: Background: TGF-β acts as a suppressor of primary tumor initiation but has been implicated as a promoter of the later malignant stages. Here associations with risk of invasive breast cancer are assessed for single-nucleotide polymorphisms (SNP) tagging 17 genes in the canonical TGF-β ALK5/SMADs 2&3 and ALK1/SMADs 1&5 signaling pathways: LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, and SMAD7 [Approved Human Gene Nomenclature Committee gene names: ACVRL1 (for ALK1) and ENG (for Endoglin)].Methods: Three-hundred-fifty-four tag SNPs (minor allele frequency > 0.05) were selected for genotyping in a staged study design using 6,703 cases and 6,840 controls from the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) study. Significant associations were meta-analyzed with data from the NCI Polish Breast Cancer Study (PBCS; 1,966 cases and 2,347 controls) and published data from the Breast Cancer Association Consortium (BCAC).Results: Associations of three SNPs, tagging TGFB1 (rs1982073), TGFBR1 (rs10512263), and TGFBR2 (rs4522809), were detected in SEARCH; however, associations became weaker in meta-analyses including data from PBCS and BCAC. Tumor subtype analyses indicated that the TGFB1 rs1982073 association may be confined to increased risk of developing progesterone receptor negative (PR−) tumors [1.18 (95% CI: 1.09–1.28), 4.1 × 10−5 (P value for heterogeneity of ORs by PR status = 2.3 × 10−4)]. There was no evidence for breast cancer risk associations with SNPs in the endothelial-specific pathway utilizing ALK1/SMADs 1&5 that promotes angiogenesis.Conclusion: Common variation in the TGF-β ALK5/SMADs 2&3 signaling pathway, which initiates signaling at the cell surface to inhibit cell proliferation, might be related to risk of specific tumor subtypes.Impact: The subtype specific associations require very large studies to be confirmed. Cancer Epidemiol Biomarkers Prev; 20(6); 1112–9. ©2011 AACR.
Published: 2023
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9. Supplementary Table 1 from Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor–Positive, Lower Grade Breast Cancer

Author: Douglas F. Easton, Georgia Chenevix-Trench, Qin Wang, Manjeet K. Humphreys, Xianshu Wang, Janet E. Olson, Albina Farahtdinova, Darya Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Madeleine Tilanus-Linthorst, Rogier A. Oldenburg, Antoinette Hollestelle, Maartje Hooning, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Christina Justenhoven, Volker Harth, Ute Hamann, Jonathan Beesley, Xiaoqing Chen, Sara Lindstrom, Peter Kraft, Susan E. Hankinson, David J. Hunter, Sei-Hyun Ahn, Dong-Young Noh, Keun-Young Yoo, Daehee Kang, Katarzyna Durda, Katarzyna Jaworska, Jan Lubinski, Anna Jakubowska, Barbara Burwinkel, Christof Sohn, Andreas Schneeweiss, Frederik Marme, Karen A. Pooley, Alison M. Dunning, Paul D.P. Pharoah, Rob A.E.M. Tollenaar, Laura J. Van ‘t Veer, Annegien Broeks, Marjanka K. Schmidt, Nicola Miller, Michael Kerin, Ian Tomlinson, Elinor Sawyer, Argyrios Ziogas, Hoda Anton-Culver, Dieter Flesch-Janys, Stefan Nickels, Julian Peto, Isabel dos Santos Silva, Lorna J. Gibson, Olivia Fletcher, Robert N. Hoover, Gilles D. Thomas, Rita K. Schmutzler, Claus R. Bartram, Joerg Heil, Alfons Meindl, Jaana M. Hartikainen, Veli-Matti Kosma, Vesa Kataja, Arto Mannermaa, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Matthias W. Beckmann, Arif B. Ekici, Christian M. Bayer, Peter A. Fasching, Yuri I. Rogov, Iosif V. Zalutsky, Natalia N. Antonenkova, Natalia V. Bogdanova, Jonine D. Figueroa, Mark E. Sherman, Jolanta Lissowska, Stephen J. Chanock, Alexander Miron, Esther M. John, Laura Baglietto, Graham G. Giles, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Shan Wang-Gohrke, Jenny Chang-Claude, James McKay, Paul Brennan, Valerie Gaborieau, Suleeporn Sangrajrang, Karin Leunen, Giuseppe Floris, Betül T. Yesilyurt, Diether Lambrechts, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Anne-Lise Børrensen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Charlotte Lanng, Stig E. Bojesen, Børge G. Nordestgaard, Ming-Feng Hou, Chiun-Sheng Huang, Jyh-Cherng Yu, Chen-Yang Shen, Nazneen Rahman, Anthony Renwick, Clare Turnbull, Sheila Seal, Simon S. Cross, Graeme Elliot, Ian W. Brock, Angela Cox, Peter Hillemanns, Johann H. Karstens, Peter Schürmann, Thilo Dörk, Javier Benítez, Jose Ignacio Arias Pérez, M. Pilar Zamora, Núria Malats, Zachary Fredericksen, Rebecca Hein, Gianluca Severi, Fergus J. Couch, Montserrat García-Closas, Ellen L. Goode, and Roger L. Milne
Abstract: PDF file - 137K
Published: 2023
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10. Supplementary Tables 1-13 from 19p13.1 Is a Triple-Negative–Specific Breast Cancer Susceptibility Locus

Author: Fergus J. Couch, Douglas F. Easton, Ylermi Soini, Jaana M. Hartikainen, Veli-Matti Kosma, Arto Mannermaa, Xiaoqing Chen, Jonathan Beesley, Georgia Chenevix-Trench, Marie-Rose Christiaens, Anne-Sophie Dieudonne, Sigrid Hatse, Diether Lambrechts, Monica Barile, Siranoush Manoukian, Paolo Peterlongo, Paolo Radice, Janet E. Olson, Susan Slager, V.S. Pankratz, Matthew L. Kosel, Gianluca Severi, Catriona A. McLean, Laura Baglietto, Graham G. Giles, Anne-Lise Børresen-Dale, Vessela Kristensen, Grethe Grenaker Alnæs, Alexander Miron, Esther M. John, Mervi Grip, Arja Jukkola-Vuorinen, Katri Pylkäs, Robert Winqvist, Anna Marie Mulligan, Gord Glendon, Julia A. Knight, Irene L. Andrulis, Maartje J. Hooning, Rob A.E.M. Tollenaar, Caroline Seynaeve, Peter Devilee, Jolanta Lissowska, Mark E. Sherman, Jonine D. Figueroa, Montserrat Garcia-Closas, Diana M. Eccles, Helena Hwang, Foluso Ademuyiwa, Christine B. Ambrosone, Kamila Czene, Per Hall, Malcom W. Reed, Simon S. Cross, Angela Cox, Qin Wang, Manjeet K. Humphreys, Alison M. Dunning, Paul P. Pharoah, Hans Ulrich Ulmer, Thomas Rüdiger, Thomas Dünnebier, Ute Hamann, Chia-Ni Hsiung, Huan-Ming Hsu, Jyh-Cherng Yu, Chen-Yang Shen, Christina Clarke Dur, Leslie Bernstein, Argyrios Ziogas, Hoda Anton-Culver, Minouk J. Schoemaker, Nicholas Orr, Alan Ashworth, Anthony J. Swerdlow, Melissa C. Southey, Daniel J. Park, Carmel Apicella, John L. Hopper, Efraim H. Rosenberg, Linde M. Braaf, Annegien Broeks, Marjanka K. Schmidt, Surapon Wiangnon, Puttisak Puttawibul, Kenneth Muir, Artitaya Lophatananon, Arif B. Ekici, Arndt Hartmann, Matthias W. Beckmann, Peter A. Fasching, Isabel dos Santos Silva, Olivia Fletcher, Nichola Johnson, Julian Peto, Michael J. Kerin, Ian Tomlinson, Elinor Sawyer, Christof Sohn, Andreas Schneeweiss, Frederick Marmé, Barbara Burwinkel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Pascal Guénel, Henrik Flyger, Børge G. Nordestgaard, Sune F. Nielsen, Stig E. Bojesen, José Ignacio Arias Pérez, María Pilar Zamora, Javier Benítez, Roger L. Milne, Annie Perkins, Miriam Dwek, Ruth Swann, Helen J. Gogas, George Fountzilas, Alexandra Stavropoulou, Drakoulis Yannoukakos, Penelope Miron, Christa Stegmaier, Volker Arndt, Heiko Müller, Hermann Brenner, Priyanka Sharma, Harsh B. Pathak, JoEllen Weaver, Andrew K. Godwin, Christoph Engel, Sarah Schott, Claus R. Bartram, Alfons Meindl, Rita K. Schmutzler, Hans-Peter Fischer, Yon-Dschun Ko, Hiltrud Brauch, Stefan Nickels, Shan Wang-Gohrke, Hans-Peter Sinn, Dieter Flesch-Janys, Alina Vrieling, Jenny Chang-Claude, Carl Blomqvist, Kristiina Aittomäki, Dario Greco, Heli Nevanlinna, Annika Lindblom, Sara Margolin, Xianshu Wang, Celine M. Vachon, Zachary Fredericksen, and Kristen N. Stevens
Abstract: PDF file - 272K
Published: 2023
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11. Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk.

Author: Mia M Gaudet, Karoline B Kuchenbaecker, Joseph Vijai, Robert J Klein, Tomas Kirchhoff, Lesley McGuffog, Daniel Barrowdale, Alison M Dunning, Andrew Lee, Joe Dennis, Sue Healey, Ed Dicks, Penny Soucy, Olga M Sinilnikova, Vernon S Pankratz, Xianshu Wang, Ronald C Eldridge, Daniel C Tessier, Daniel Vincent, Francois Bacot, Frans B L Hogervorst, Susan Peock, Dominique Stoppa-Lyonnet, KConFab Investigators, Paolo Peterlongo, Rita K Schmutzler, Katherine L Nathanson, Marion Piedmonte, Christian F Singer, Mads Thomassen, Ontario Cancer Genetics Network, Thomas v O Hansen, Susan L Neuhausen, Ignacio Blanco, Mark H Greene, Judith Garber, Jeffrey N Weitzel, Irene L Andrulis, David E Goldgar, Emma D'Andrea, Trinidad Caldes, Heli Nevanlinna, Ana Osorio, Elizabeth J van Rensburg, Adalgeir Arason, Gad Rennert, Ans M W van den Ouweland, Annemarie H van der Hout, Carolien M Kets, Cora M Aalfs, Juul T Wijnen, Margreet G E M Ausems, HEBON, EMBRACE, Debra Frost, Steve Ellis, Elena Fineberg, Radka Platte, D Gareth Evans, Chris Jacobs, Julian Adlard, Marc Tischkowitz, Mary E Porteous, Francesca Damiola, GEMO Study Collaborators, Lisa Golmard, Laure Barjhoux, Michel Longy, Muriel Belotti, Sandra Fert Ferrer, Sylvie Mazoyer, Amanda B Spurdle, Siranoush Manoukian, Monica Barile, Maurizio Genuardi, Norbert Arnold, Alfons Meindl, Christian Sutter, Barbara Wappenschmidt, Susan M Domchek, Georg Pfeiler, Eitan Friedman, Uffe Birk Jensen, Mark Robson, Sohela Shah, Conxi Lazaro, Phuong L Mai, Javier Benitez, Melissa C Southey, Marjanka K Schmidt, Peter A Fasching, Julian Peto, Manjeet K Humphreys, Qin Wang, Kyriaki Michailidou, Elinor J Sawyer, Barbara Burwinkel, Pascal Guénel, Stig E Bojesen, Roger L Milne, Hermann Brenner, Magdalena Lochmann, GENICA Network, Kristiina Aittomäki, Thilo Dörk, Sara Margolin, Arto Mannermaa, Diether Lambrechts, Jenny Chang-Claude, Paolo Radice, Graham G Giles, Christopher A Haiman, Robert Winqvist, Peter Devillee, Montserrat García-Closas, Nils Schoof, Maartje J Hooning, Angela Cox, Paul D P Pharoah, Anna Jakubowska, Nick Orr, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Per Hall, Fergus J Couch, Jacques Simard, David Altshuler, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou, and Kenneth Offit
Subjects: Genetics, QH426-470
Abstract: Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9 × 10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer.
Published: 2013
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12. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

Author: Stefan Nickels, Thérèse Truong, Rebecca Hein, Kristen Stevens, Katharina Buck, Sabine Behrens, Ursula Eilber, Martina Schmidt, Lothar Häberle, Alina Vrieling, Mia Gaudet, Jonine Figueroa, Nils Schoof, Amanda B Spurdle, Anja Rudolph, Peter A Fasching, John L Hopper, Enes Makalic, Daniel F Schmidt, Melissa C Southey, Matthias W Beckmann, Arif B Ekici, Olivia Fletcher, Lorna Gibson, Isabel dos Santos Silva, Julian Peto, Manjeet K Humphreys, Jean Wang, Emilie Cordina-Duverger, Florence Menegaux, Børge G Nordestgaard, Stig E Bojesen, Charlotte Lanng, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Hiltrud Brauch, Thomas Brüning, Volker Harth, Genica Network, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, kConFab, AOCS Management Group, Diether Lambrechts, Dominiek Smeets, Patrick Neven, Robert Paridaens, Dieter Flesch-Janys, Nadia Obi, Shan Wang-Gohrke, Fergus J Couch, Janet E Olson, Celine M Vachon, Graham G Giles, Gianluca Severi, Laura Baglietto, Kenneth Offit, Esther M John, Alexander Miron, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Stephen J Chanock, Jolanta Lissowska, Jianjun Liu, Angela Cox, Helen Cramp, Dan Connley, Sabapathy Balasubramanian, Alison M Dunning, Mitul Shah, Amy Trentham-Dietz, Polly Newcomb, Linda Titus, Kathleen Egan, Elizabeth K Cahoon, Preetha Rajaraman, Alice J Sigurdson, Michele M Doody, Pascal Guénel, Paul D P Pharoah, Marjanka K Schmidt, Per Hall, Doug F Easton, Montserrat Garcia-Closas, Roger L Milne, and Jenny Chang-Claude
Subjects: Genetics, QH426-470
Abstract: Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of
Published: 2013
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13. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).

Author: Rebecca Hein, Melanie Maranian, John L Hopper, Miroslaw K Kapuscinski, Melissa C Southey, Daniel J Park, Marjanka K Schmidt, Annegien Broeks, Frans B L Hogervorst, H Bas Bueno-de-Mesquita, Kenneth R Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Puttisak Puttawibul, Peter A Fasching, Alexander Hein, Arif B Ekici, Matthias W Beckmann, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Frederick Marmee, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Roger L Milne, Jose Ignacio Arias Perez, M Pilar Zamora, Javier Benítez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Nazneen Rahman, Sheila Seal, Clare Turnbull, Anthony Renwick, Alfons Meindl, Sarah Schott, Claus R Bartram, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, GENICA Network, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia V Bogdanova, Iosif V Zalutsky, Natalia N Antonenkova, Marina Bermisheva, Darya Prokovieva, Albina Farahtdinova, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana Hartikainen, Xiaoqing Chen, Jonathan Beesley, Kconfab Investigators, AOCS Group, Diether Lambrechts, Hui Zhao, Patrick Neven, Hans Wildiers, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus J Couch, Janet E Olson, Xianshu Wang, Zachary Fredericksen, Graham G Giles, Laura Baglietto, Catriona A McLean, Gianluca Severi, Kenneth Offit, Mark Robson, Mia M Gaudet, Joseph Vijai, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børresen-Dale, Esther M John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Jonine D Figueroa, Montserrat García-Closas, Jolanta Lissowska, Mark E Sherman, Maartje Hooning, John W M Martens, Caroline Seynaeve, Margriet Collée, Per Hall, Keith Humpreys, Kamila Czene, Jianjun Liu, Angela Cox, Ian W Brock, Simon S Cross, Malcolm W R Reed, Shahana Ahmed, Maya Ghoussaini, Paul D P Pharoah, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen-Yang Shen, Jyh-Cherng Yu, Huan-Ming Hsu, Ming-Feng Hou, Nick Orr, Minouk Schoemaker, Alan Ashworth, Anthony Swerdlow, Amy Trentham-Dietz, Polly A Newcomb, Linda Titus, Kathleen M Egan, Georgia Chenevix-Trench, Antonis C Antoniou, Manjeet K Humphreys, Jonathan Morrison, Jenny Chang-Claude, Douglas F Easton, and Alison M Dunning
Subjects: Medicine, Science
Abstract: The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.
Published: 2012
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14. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

Author: Tomas Kirchhoff, Mia M Gaudet, Antonis C Antoniou, Lesley McGuffog, Manjeet K Humphreys, Alison M Dunning, Stig E Bojesen, Børge G Nordestgaard, Henrik Flyger, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Thilo Dork, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Fergus J Couch, Janet Olson, Celine Vachon, Xianshu Wang, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W R Reed, Barbara Burwinkel, Alfons Meindl, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, GENICA Network, Annegien Broeks, Marjanka K Schmidt, Laura J Van 't Veer, Linde M Braaf, Nichola Johnson, Olivia Fletcher, Lorna Gibson, Julian Peto, Clare Turnbull, Sheila Seal, Anthony Renwick, Nazneen Rahman, Pei-Ei Wu, Jyh-Cherng Yu, Chia-Ni Hsiung, Chen-Yang Shen, Melissa C Southey, John L Hopper, Fleur Hammet, Thijs Van Dorpe, Anne-Sophie Dieudonne, Sigrid Hatse, Diether Lambrechts, Irene L Andrulis, Natalia Bogdanova, Natalia Antonenkova, Juri I Rogov, Daria Prokofieva, Marina Bermisheva, Elza Khusnutdinova, Christi J van Asperen, Robert A E M Tollenaar, Maartje J Hooning, Peter Devilee, Sara Margolin, Annika Lindblom, Roger L Milne, José Ignacio Arias, M Pilar Zamora, Javier Benítez, Gianluca Severi, Laura Baglietto, Graham G Giles, kConFab, AOCS Study Group, Amanda B Spurdle, Jonathan Beesley, Xiaoqing Chen, Helene Holland, Sue Healey, Shan Wang-Gohrke, Jenny Chang-Claude, Arto Mannermaa, Veli-Matti Kosma, Jaana Kauppinen, Vesa Kataja, Bjarni A Agnarsson, Maria A Caligo, Andrew K Godwin, Heli Nevanlinna, Tuomas Heikkinen, Zachary Fredericksen, Noralane Lindor, Katherine L Nathanson, Susan M Domchek, SWE-BRCA, Niklas Loman, Per Karlsson, Marie Stenmark Askmalm, Beatrice Melin, Anna von Wachenfeldt, HEBON, Frans B L Hogervorst, Martijn Verheus, Matti A Rookus, Caroline Seynaeve, Rogier A Oldenburg, Marjolijn J Ligtenberg, Margreet G E M Ausems, Cora M Aalfs, Hans J P Gille, Juul T Wijnen, Encarna B Gómez García, EMBRACE, Susan Peock, Margaret Cook, Clare T Oliver, Debra Frost, Craig Luccarini, Gabriella Pichert, Rosemarie Davidson, Carol Chu, Diana Eccles, Kai-Ren Ong, Jackie Cook, Fiona Douglas, Shirley Hodgson, D Gareth Evans, Rosalind Eeles, Bert Gold, Paul D P Pharoah, Kenneth Offit, Georgia Chenevix-Trench, Douglas F Easton, and BCAC/CIMBA
Subjects: Medicine, Science
Abstract: Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p =
Published: 2012
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15. Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls

Author: Joe Dennis, Sarah Stewart-Brown, Per Hall, Hui Cai, Pei Ei Wu, Soo Chin Lee, Alison M. Dunning, Kenneth Muir, Wenjin Wang, Min Hyuk Lee, Francois Bacot, Hyuna Sung, Chiu-Chen Tseng, Zefang Ren, Hidemi Ito, Artitaya Lophatananon, Ben Zhang, Wei Lu, Kexin Chen, Jong Won Lee, Daniel O. Stram, Mi Kyung Kim, Wonshik Han, Chiun-Sheng Huang, Soo Hwang Teo, Ji Yeob Choi, David Van Den Berg, Hui Miao, Xiao-Ou Shu, Jiajun Shi, Wei Zheng, Mikael Hartman, Hongbing Shen, Jirong Long, Douglas F. Easton, Qin Wang, Javier Benitez, Chun Li, Hideo Tanaka, Jyh Cherng Yu, Bu Tian Ji, Motoki Iwasaki, Daniel C. Tessier, Thomas C. Putti, Daniel Vincent, Tien Yin Wong, Ming-Feng Hou, Ui-Soon Khoo, Keitaro Matsuo, Cheng Har Yip, Hiroji Iwata, Keun-Young Yoo, Dong Young Noh, Paul D.P. Pharoah, Anna H. Wu, Sung-Won Kim, In Nee Kang, Yong-Bing Xiang, Ying Zheng, Wanqing Wen, Jong-Young Lee, Pornthep Siriwanarangsan, Chen-Yang Shen, Suleeporn Sangrajrang, Daehee Kang, Aiko Sueta, Yu Tang Gao, Qiuyin Cai, Kyriaki Michailidou, Manjeet K. Humphreys, Sue K. Park, and Christopher A. Haiman
Subjects: Adult, Oncology, China, medicine.medical_specialty, Population, Estrogen receptor, Breast Neoplasms, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Asian People, Internal medicine, Republic of Korea, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Molecular Biology, Genetics (clinical), Aged, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, Association Studies Articles, Case-control study, Cancer, General Medicine, Middle Aged, medicine.disease, 3. Good health, Receptors, Estrogen, Case-Control Studies, 030220 oncology & carcinogenesis, Female, Genome-Wide Association Study
Abstract: In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of, published_or_final_version
Published: 2013
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16. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium

Author: Javier Benitez, Frederik Marmé, Nichola Johnson, Ian W. Brock, Fiona M. Blows, Natalia Bogdanova, Arto Mannermaa, Peter Hillemanns, Hoda Anton-Culver, Anthony J. Swerdlow, Roger L. Milne, Jonathan Beesley, Veli-Matti Kosma, Guzel Zinnatullina, Paolo Peterlongo, Irene L. Andrulis, Annika Lindblom, Dieter Flesch-Janys, Ann Smeets, Arif B. Ekici, Pascal Guénel, Vesa Kataja, Thomas Brüning, Graham G. Giles, Isabel dos-Santos-Silva, Douglas F. Easton, Yuriy Rogov, Ruediger Schulz-Wendtland, Pierre Laurent-Puig, Thilo Dörk, Malcolm W.R. Reed, Heiko Müller, Linda M. Braaf, Janet E. Olson, Cariona A. McLean, Leslie Bernstein, Elinor J. Sawyer, Jaana M. Hartikainen, Siranoush Manoukian, Robert Paridaens, Marina Bermisheva, Natalia Antonenkova, Ian Tomlinson, Thérèse Truong, Minouk J. Schoemaker, Anna Marie Mulligan, Elza Khusnutdinova, Xianshu Wang, Christof Sohn, Katri Pylkäs, Caroline M. Seynaeve, Christina Clarke Dur, Caroline Weltens, Sune F. Nielsen, Carl Blomqvist, Nick Orr, Hiltrud Brauch, Maryam Mahmoodi, Shan Wang-Gohrke, Melissa C. Southey, Fergus J. Couch, Olivia Fletcher, Mervi Grip, Nayana Weerasooriya, Georgia Chenevix-Trench, Rita K. Schmutzler, Julian Peto, Jenny Chang-Claude, Peter Schürmann, Frank Dudbridge, John W.M. Martens, Robert Winqvist, Surapon Wiangnon, Celine M. Vachon, Arkom Chaiwerawattana, Hermann Brenner, Artitaya Lophatananon, Arja Jukkola-Vuorinen, Peter A. Fasching, Børge G. Nordestgaard, Manjeet K. Humphreys, Barbara Burwinkel, Kristiina Aittomäki, Marjanka K. Schmidt, Argyrios Ziogas, Michael Bremer, Paul D.P. Pharoah, Loris Bernard, Alexander Miron, Sara Margolin, Kamila Czene, Diether Lambrechts, Claus R. Bartram, Annegien Broeks, Maya Ghoussaini, John L. Hopper, Simon S. Cross, Matthias W. Beckmann, Per Hall, Agnes Jager, Stig E. Bojesen, Michael Jones, Darya Prokofyeva, Julia A. Knight, Alan Ashworth, Taru A. Muranen, Xiaoqing Chen, Esther M. John, Claire Mulot, Alfons Meindl, Ursula Eilber, Laura Baglietto, José Ignacio Arias-Perez, Peter Devilee, Henrik Flyger, Sten Cornelissen, Jingmei Li, Katharina Buck, Carmel Apicella, Michael J. Kerin, Gianluca Severi, Alison M. Dunning, Kenneth Muir, Anne Langheinz, Andreas Schneeweiss, Heli Nevanlinna, Michael Golatta, Christina Justenhoven, Antoinette Hollestelle, Jianjun Liu, Helen R. Warren, Sabine Behrens, Madeleine M.A. Tilanus-Linthorst, Angela Cox, Maartje J. Hooning, Qin Wang, Paolo Radice, Volker Arndt, Robert A.E.M. Tollenaar, M. Pilar Zamora, Medical Oncology, Surgery, and Clinical Genetics
Subjects: Oncology, Pathology, Epidemiology, Estrogen receptor, population, Genome-wide association study, genetic risk, 0302 clinical medicine, Receptors, common variants, Progesterone, 0303 health sciences, education.field_of_study, identifies 2, Chromosome Mapping, Single Nucleotide, Middle Aged, 5p12, 3. Good health, Receptors, Estrogen, 030220 oncology & carcinogenesis, alleles, Female, Chromosomes, Human, Pair 9, Receptors, Progesterone, linkage, Human, Pair 9, medicine.medical_specialty, Population, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Chromosomes, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Polymorphism, Allele, education, Aged, 030304 developmental biology, menarche, Case-control study, Cancer, medicine.disease, confer susceptibility, Estrogen, Case-Control Studies, genome-wide association, Genome-Wide Association Study
Abstract: Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10−29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10−143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10−22) but less strongly, if at all, with ER-negative (ER−) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10−6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783–. ©2012 AACR.
Published: 2016

17. 11q13 is a susceptibility locus for hormone receptor positive breast cancer

Author: Dong Young Noh, Pascal Guénel, Graeme Elliott, Vesa Kataja, Shamil Gancev, Xianshu Wang, Shan Wang-Gohrke, Annegien Broeks, Florence Menegaux, Hans Wildiers, Richard van Hien, Natalia Bogdanova, Jean Wang, Puttisak Puttawibul, Betül T. Yesilyurt, Peter Devilee, Gord Glendon, Katri Pylkäs, Mark E. Sherman, Jenny Chang-Claude, Federik Marme, Michael Bremer, Katarzyna Durda, Sarah Schott, Vessela N. Kristensen, Paolo Radice, Teresa Selander, Kamila Czene, Alfons Meindl, Gianluca Severi, Angela Cox, Maartje J. Hooning, Claus R. Bartram, John L. Hopper, Ursel Eilber, Michael Jones, M. Pilar Zamora, Stephen J. Chanock, Laura Baglietto, Caroline M. Seynaeve, Daehee Kang, Thilo Dörk, Rita K. Schmutzler, Julian Peto, Børge G. Nordestgaard, Loris Bernard, Stig E. Bojesen, Barbara Burwinkel, Douglas F. Easton, Arif B. Ekici, kConFab Investigators, Mervi Grip, Robert A.E.M. Tollenaar, Argyrios Ziogas, Jonathan Beesley, Paolo Peterlongo, Volker Arndt, Xiaoqing Chen, Nichola Johnson, Jaana M. Hartikainen, Ming-Feng Hou, Diether Lambrechts, Ruediger Schulz-Wendtland, Jan Lubinski, Taru A. Muranen, Heli Nevanlinna, Esther M. John, Graham G. Giles, Chen-Yang Shen, Jolanta Lissowska, Ian W. Brock, Grethe I. Grenaker Alnæs, Gillian S. Dite, Charlotte Lanng, Hiltrud Brauch, Anthony J. Swerdlow, MC Southey, Christina Justenhoven, Manjeet K. Humphreys, Keun-Young Yoo, Elinor J. Sawyer, Emilie Cordina-Duverger, Jose Ignacio Arias Perez, Fergus J. Couch, Peter Schürmann, Stefan Nickels, Jianjun Liu, Marjanka K. Schmidt, Zachary S. Fredericksen, Yuri I. Rogov, Ute Hamann, Elza Khusnutdinova, Hermann Brenner, Sara Margolin, Natalia Antonenkova, Peter A. Fasching, Matthias W. Beckmann, Johann H. Karstens, Montserrat Garcia-Closas, Patrick Neven, Thomas Brüning, Carl Blomqvist, Heiko Müller, Jyh Cherng Yu, Katarzyna Jaworska, Yon Ko, Pei Ei Wu, Arto Mannermaa, Rebecca Hein, Darya Prokofieva, Melissa C. Southey, Andreas Schneeweiss, Irene L. Andrulis, Christa Stegmaier, Robert Winqvist, Annika Lindblom, Anna Jakubowska, Paul D.P. Pharoah, Peter Hillemanns, Alexander Miron, Roger L. Milne, Marina Bermisheva, Dieter Flesch-Janys, Christof Sohn, Nicola Miller, Georgia Chenevix-Trench, Kristiina Aittomäki, Ian Tomlinson, Thérèse Truong, Anna Marie Mulligan, Siranoush Manoukian, Robert Paridaens, Anne Lise Børresen-Dale, Suthee Rattanamongkongul, Olivia Fletcher, Simon S. Cross, Artitaya Lophatananon, Isabel dos Santos Silva, Janet E. Olson, Nick Orr, Per Hall, Alan Ashworth, Javier Benitez, Hoda Anton-Culver, Veli-Matti Kosma, Alison M. Dunning, Kenneth Muir, Sten Cornelissen, Carmel Apicella, Arja Jukkola-Vuorinen, Michael J. Kerin, ~, and Medical Oncology
Subjects: Oncology, hormone receptor status, Estrogen receptor, Genome-wide association study, 0302 clinical medicine, Risk Factors, Genotype, Receptors, single-nucleotide polymorphisms, common variants, Pair 11, Progesterone, Genetics (clinical), Genetics, 0303 health sciences, repair genes, Single Nucleotide, identifies 5, 11q13, Breast cancer susceptibility, Genome-wide association, Hormone receptor status, Polymorphisms, Risk factors, Breast Neoplasms, Chromosomes, Human, Pair 11, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, 3. Good health, ovarian-cancer, 030220 oncology & carcinogenesis, Human, brca1 mutations, medicine.medical_specialty, Single-nucleotide polymorphism, Biology, Chromosomes, Article, White People, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Progesterone receptor, medicine, Polymorphism, 030304 developmental biology, breast cancer susceptibility, Odds ratio, tumor characteristics, medicine.disease, confer susceptibility, Estrogen, genome-wide association, family registry, Ovarian cancer, polymorphisms
Abstract: Journal article A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P â ¤ 3 Ã 10(-9) ) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 Ã 10(-39) ). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype. EC Seventh Framework Programme - grant number HEALTH-F2-2009-223175 peer-reviewed
Published: 2016
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18. 19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus

Author: Linde M. Braaf, Andreas Schneeweiss, Alexandra V. Stavropoulou, Elinor J. Sawyer, Christoph Engel, Pascal Guénel, Hans Ulrich Ulmer, Efraim H. Rosenberg, Mervi Grip, Hans-Peter Sinn, Chen-Yang Shen, Daniel J. Park, Monica Barile, Annie Perkins, Xianshu Wang, Susan L. Slager, Leslie Bernstein, José Ignacio Arias Peŕez, Puttisak Puttawibul, Gianluca Severi, Helen Gogas, Diana Eccles, Sara Margolin, Michael J. Kerin, Carl Blomqvist, Irene L. Andrulis, Minouk J. Schoemaker, Dario Greco, Javier Benitez, Matthias W. Beckmann, Maria Pilar Zamora, Qin Wang, Diether Lambrechts, Hoda Anton-Culver, Foluso O. Ademuyiwa, Veli-Matti Kosma, Mark E. Sherman, Anne Sophie Dieudonne, F Marmé, Helena Hwang, Peter Devilee, Shan Wang-Gohrke, Alina Vrieling, Melissa C. Southey, Annika Lindblom, Paolo Radice, Penelope Miron, Theŕeśe Truong, Per Hall, Douglas F. Easton, Siranoush Manoukian, Drakoulis Yannoukakos, Rita K. Schmutzler, Vessela N. Kristensen, Julian Peto, Jonathan Beesley, Arndt Hartmann, Priyanka Sharma, Alison M. Dunning, Paolo Peterlongo, Christine B. Ambrosone, Henrik Flyger, Nichola Johnson, Jonine D. Figueroa, Barbara Burwinkel, Kenneth Muir, Roger L. Milne, Sigrid Hatse, Julia A. Knight, Ylermi Soini, Alan Ashworth, Artitaya Lophatananon, Robert Winqvist, Alfons Meindl, Thomas Rüdiger, George Fountzilas, Annegien Broeks, Simon S. Cross, Rob A. E. M. Tollenaar, Paul D.P. Pharoah, Alexander Miron, Montserrat Garcia-Closas, Laura Baglietto, Matthew L. Kosel, Arif B. Ekici, Heiko Müller, Jyh Cherng Yu, Grethe Grenaker Alnsæ, Argyrios Ziogas, Thomas Dünnebier, Ian Tomlinson, Anna Marie Mulligan, Ruth Swann, Chia-Ni Hsiung, Sarah Schott, Christina Clarke Dur, Catriona McLean, Georgia Chenevix-Trench, Caroline Seynaeve, Hiltrud Brauch, Orr Nicholas, Carmel Apicella, Vernon S. Pankratz, Olivia Fletcher, Surapon Wiangnon, Arja Jukkola-Vuorinen, Anne Lise Brøresen-Dale, Dieter Flesch-Janys, Fergus J. Couch, Peter A. Fasching, Brøge G. Nordestgaard, Kristiina Aittomäki, Marie Rose Christiaens, Jaana M. Hartikainen, Manjeet K. Humphreys, Ute Hamann, Marjanka K. Schmidt, Isabel dos Santos Silva, Harsh B. Pathak, Janet E. Olson, Jenny Chang-Claude, Graham G. Giles, Miriam Dwek, Stig E. Bojesen, Florence Menegaux, Christa Stegmaier, Katri Pylkäs, Huan Ming Hsu, Sune F. Nielsen, Christof Sohn, Kamila Czene, Claus R. Bartram, Jo Ellen Weaver, John L. Hopper, Xiaoqing Chen, Emilie Cordina-Duverger, Stefan Nickels, Esther M. John, Heli Nevanlinna, Jolanta Lissowska, Zachary S. Fredericksen, Angela Cox, Maartje J. Hooning, Volker Arndt, MW Reed, Celine M. Vachon, Yon Ko, Anthony J. Swerdlow, Gord Glendon, Hans Fischer, Arto Mannermaa, Kristen N. Stevens, Hermann Brenner, Andrew K. Godwin, Clinical Genetics, and Medical Oncology
Subjects: Oncology, Cancer Research, Receptor, ErbB-2, population, Estrogen receptor, consortium, Genome-wide association study, brca1, ErbB-2, 0302 clinical medicine, common variants, Receptors, risk-factors, skin and connective tissue diseases, Progesterone, Triple-negative breast cancer, 0303 health sciences, education.field_of_study, Chromosome Mapping, 3. Good health, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, complex, Receptor, Human, Risk, medicine.medical_specialty, Population, Breast Neoplasms, Genetic Loci, Humans, Chromosomes, Human, Pair 19, Genetic Predisposition to Disease, Biology, Article, Chromosomes, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Progesterone receptor, medicine, Genetic predisposition, education, 030304 developmental biology, Gynecology, Pair 19, tumor subtypes, confer susceptibility, medicine.disease, Estrogen, 14q24.1 rad51l1, genome-wide association, Ovarian cancer
Abstract: The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.
Published: 2012
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19. 7q21-rs6964587 and breast cancer risk: an extended case-control study by the Breast Cancer Association Consortium

Author: Argyrios Ziogas, Alfons Meindl, Jonathan Beesley, Jianjun Liu, Georgia Chenevix-Trench, Caroline Seynaeve, Laura Baglietto, Malcolm W.R. Reed, Angela Cox, Kamila Czene, Douglas F. Easton, Arif B. Ekici, Kristiina Aittomäki, Chen-Yang Shen, John L. Hopper, Peter A. Fasching, Lorna Gibson, Núria Malats, Stig E. Bojesen, Astrid K. Irwanto, Tuomas Heikkinen, Peter Devilee, Heli Nevanlinna, Ian W. Brock, Xiaoqing Chen, Jolanta Lissowska, Ruediger Schulz-Wendtland, Henrik Flyger, Montserrat Garcia-Closas, Xianshu Wang, Justo Lorenzo-Bermejo, Jenny Chang-Claude, Zachary S. Fredericksen, Jyh Cherng Yu, Julian Peto, Børge G. Nordestgaard, Sara Margolin, Annika Lindblom, Arto Mannermaa, Letitia D. Smith, Barbara Burwinkel, Matthias W. Beckmann, Beate Pesch, Joerg Heil, José Ignacio Arias, Fergus J. Couch, Rebecca Hein, Dong Young Noh, Olivia Fletcher, Stephen J. Chanock, Ute Hamann, Graeme Elliott, Per Hall, Vesa Kataja, Pei Ei Wu, Keun-Young Yoo, Daehee Kang, Karen A. Pooley, Yon Ko, Carl Blomqvist, Dallas R. English, Mark E. Sherman, Graham G. Giles, Alina Vrieling, Roger L. Milne, Rob A. E. M. Tollenaar, Shan Wang-Gohrke, Gianluca Severi, Alison M. Dunning, Carmel Apicella, Javier Benitez, Hoda Anton-Culver, Veli-Matti Kosma, Christie J. van Asperen, Isabel dos Santos Silva, Janet E. Olson, Dieter Flesch-Janys, Bernd Frank, Melissa C. Southey, Paul D.P. Pharoah, Huan Ming Hsu, M. Pilar Zamora, Manjeet K. Humphreys, Medical Oncology, and Hematology
Subjects: Oncology, A Kinase Anchor Proteins, Logistic regression, Medical and Health Sciences, 0302 clinical medicine, Medizinische Fakultät, Risk Factors, Epidemiology, Odds Ratio, Genetics (clinical), Genetics & Heredity, Genetics, 0303 health sciences, Single Nucleotide, AOCS Group, Biological Sciences, Control subjects, 3. Good health, 030220 oncology & carcinogenesis, Pair 7, Female, GENICA Network, Chromosomes, Human, Pair 7, Human, Asian Continental Ancestry Group, medicine.medical_specialty, Alleles, Breast Neoplasms, Case-Control Studies, Cytoskeletal Proteins, European Continental Ancestry Group, Genes, Recessive, Genetic Predisposition to Disease, Humans, Logistic Models, Polymorphism, Single Nucleotide, Single-nucleotide polymorphism, Biology, Chromosomes, Article, White People, 03 medical and health sciences, Breast cancer, Asian People, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Recessive, ddc:610, Polymorphism, Allele, 030304 developmental biology, Case-control study, Odds ratio, medicine.disease, Genes
Abstract: Background: Using the Breast Cancer Association Consortium, the authors previously reported that the single nucleotide polymorphism 7q21-rs6964587 (AKAP9-M463I) is associated with breast cancer risk. The authors have now assessed this association more comprehensively using 16 independent case–control studies. Methods: The authors genotyped 14 843 invasive case patients and 19 852 control subjects with white European ancestry and 2595 invasive case patients and 2192 control subjects with Asian ancestry. ORs were estimated by logistic regression, adjusted for study. Heterogeneity in ORs was assessed by fitting interaction terms or by subclassifying case patients and applying polytomous logistic regression. Results: For white European women, the minor T allele of 7q21-rs6964587 was associated with breast cancer risk under a recessive model (OR 1.07, 95% CI 1.00 to 1.13, p=0.04). Results were inconclusive for Asian women. From a combined analysis of 24 154 case patients and 33 376 control subjects of white European ancestry from the present and previous series, the best-fitting model was recessive, with an estimated OR of 1.08 (95% CI 1.03 to 1.13, p=0.001). The OR was greater at younger ages (p trend=0.01). Conclusion: This may be the first common susceptibility allele for breast cancer to be identified with a recessive mode of inheritance.
Published: 2011
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20. 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

Author: Peter Hillemanns, Mark E. Robson, Roger L. Milne, Amanda B. Spurdle, Rob A. E. M. Tollenaar, Federik Marme, Michael Bremer, Jan Lubinski, Linda Titus-Ernstoff, Kamila Czene, Stephen J. Chanock, Mervi Grip, Graham G. Giles, Penny Webb, G. Chenevix-Trench, Natalia Bogdanova, John L. Hopper, Frances P. O'Malley, Arto Mannermaa, Mark E. Sherman, Chen-Yang Shen, Suleeporn Sangrajrang, Julian Peto, Irene L. Andrulis, Yuri I. Rogov, Annika Lindblom, Børge G. Nordestgaard, James McKay, Barbara Burwinkel, M. Pilar Zamora, José Ignacio Arias, Beate Pesch, Vijai Joseph, Shamil Hanafievich Gantcev, Fergus J. Couch, Dong Young Noh, Betül T. Yesilyurt, Jenny Chang-Claude, Ute Hamann, Vesa Kataja, Sara Margolin, Thilo Dörk, Katarzyna Jaworska, Yon Ko, Nichola Johnson, Hiltrud Brauch, Matthias W. Beckmann, Heli Nevanlinna, Malcolm W.R. Reed, Melissa C. Southey, Arif B. Ekici, Jolanta Lissowska, Isabel dos Santos Silva, Johann H. Karstens, Robert Winqvist, Shian Ling Ding, Stig E. Bojesen, Ian Tomlinson, Anna Marie Mulligan, Montserrat Garcia-Closas, Volker Harth, Katarzyna Durda, Valerie Gaborieau, Tuomas Heikkinen, Thomas Brüning, Mia M. Gaudet, Monica Barile, Sylvia Rabstein, Christina Justenhoven, Anna Jakubowska, Paul D.P. Pharoah, Jonathan Beesley, Hermann Brenner, Elza Khusnutdinova, Heiko Müller, Jyh Cherng Yu, Adam M. Lee, Paolo Peterlongo, Clare Turnbull, Doug Easton, Radka Platte, Keun-Young Yoo, J. Margriet Collée, Paolo Radice, Laura Baglietto, Sei Hyun Ahn, Paul Brennan, Olivia Fletcher, Fleur Hammet, Ans M.W. van den Ouweland, Catriona Maclean, Carl Blomqvist, Sheila Seal, Peter Schürmann, Natalia Antonenkova, Katri Pylkäs, Angela Cox, Kenneth Offit, Huan Ming Hsu, Arja Jukkola-Vuorinen, Maartje J. Hooning, Peter A. Fasching, Alison M. Dunning, Nick Orr, Volker Arndt, Javier Benitez, Diether Lambrechts, Robert B. Diasio, Manjeet K. Humphreys, Ian W. Brock, Marjanka K. Schmidt, Per Hall, Hoda Anton-Culver, Anthony J. Swerdlow, Jonine D. Figueroa, Julia A. Knight, Ylermi Soini, Alan Ashworth, Veli-Matti Kosma, Anna deFazio, Reiner Strick, Darya Prokofieva, Shan Wang-Gohrke, Polly A. Newcomb, Dorota M. Gertig, Henrik Flyger, David D.L. Bowtell, Laura J. van't Veer, John W.M. Martens, Carmel Apicella, Anthony Renwick, Andreas Schneeweiss, Michael J. Kerin, Christian Baisch, Xianshu Wang, Kathleen Egan, Argyrios Ziogas, A. Green, Marina Bermisheva, Christof Sohn, Stéphanie Peeters, Daehee Kang, Rebecca Hein, Nazneen Rahman, Annegien Broeks, Georgia Chenevix-Trench, Elinor J. Sawyer, Louise A. Brinton, Michael Jones, Xiaoqing Chen, Kristiina Aittomäki, Esther M. John, Siranoush Manoukian, Hand Peter Fischer, Amy Trentham-Dietz, Simon S. Cross, Marie Rose Chrisiaens, Gianluca Severi, Medical Oncology, and Clinical Genetics
Subjects: Oncology, Receptor, ErbB-2, 6q25.1, Estrogen receptor, Genome-wide association study, Alleles, Breast Neoplasms, Case-Control Studies, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 14, Confidence Intervals, DNA-Binding Proteins, Female, Genetic Heterogeneity, Genetic Predisposition to Disease, Humans, Odds Ratio, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, Risk Factors, Genome-Wide Association Study, Molecular Biology, Genetics, Genetics (clinical), brca1, 0302 clinical medicine, ErbB-2, Receptors, glucose, mutation carriers, Progesterone, 0303 health sciences, Association Studies Articles, General Medicine, Single Nucleotide, 3. Good health, 030220 oncology & carcinogenesis, Pair 1, metaanalysis, Human, Receptor, medicine.medical_specialty, Single-nucleotide polymorphism, Biology, Chromosomes, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, SNP, Polymorphism, 030304 developmental biology, Genetic heterogeneity, Pair 14, Case-control study, Odds ratio, confer susceptibility, medicine.disease, Estrogen, susceptibility loci, Immunology, genome-wide association, polymorphisms
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 x 10 25]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P = 6.7 x 10 23) 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: 2011
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21. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

Author: Gillian S. Dite, Brian E. Henderson, U Hamann, Rulla M. Tamimi, Agnes Jager, Laurence N. Kolonel, J Heinz, Hans Wildiers, Celine M. Vachon, Päivi Heikkilä, Chen-Yang Shen, Laura J. Van 'T Veer, Pasi Hirvikoski, Suleeporn Sangrajrang, James McKay, Päivi Auvinen, Michael Bremer, Ann Smeets, Kamila Czene, William J. Tapper, Peter Hillemanns, Fergus J. Couch, John L. Hopper, Douglas F. Easton, Jose Ignacio Arias Perez, Roger L. Milne, Helen Tsimiklis, Carmel Apicella, Antoinette Hollestelle, Zachary S. Fredericksen, Argyrios Ziogas, Helen Cramp, Melissa C. Southey, Malcolm W.R. Reed, Tjoung Won Park-Simon, Janet E. Olson, Primitiva Menéndez Rodríguez, Robert Winqvist, Fabrice Odefrey, Bohdan Górski, Caroline Seynaeve, Matthew L. Kosel, Valerie Gaborieau, Mia M. Gaudet, Diether Lambrechts, Anna Jakubowska, Paul D.P. Pharoah, Fleur Hammet, Amanda B. Spurdle, Stig E. Bojesen, Thilo Dörk, Victoria Cafourek, Julia A. Knight, Frances P O'Malley, Daniel Connley, Letitia D. Smith, David L. Wachter, Flora E. van Leeuwen, David Dynnes Ørsted, Helene Holland, Sabapathy P. Balasubramanian, Aysun Ay, Tuomas Heikkinen, Jaana M. Kauppinen, Diljit Kaur-Knudsen, Børge G. Nordestgaard, Gord Glendon, Paul Brennan, Jacek Gronwald, Mervi Grip, Elinor J. Sawyer, Kristy Driver, Jan Lubinski, Hoda Anton-Culver, Louise A. Brinton, Veli-Matti Kosma, Mieke Kriege, P. E.A. Huijts, Irene L. Andrulis, P. Zamora, S. Chanock, Pei Ei Wu, Tomasz Byrski, Arja Jukkola-Vuorinen, Peter A. Fasching, Tomasz Huzarski, Hatef Darabi, Andreas Meyer, Raem Tollenaar, Fiona M. Blows, Ian Tomlinson, Xiaohong R. Yang, Dallas R. English, Diana Eccles, Ans M.W. van den Ouweland, Johann H. Karstens, Montserrat Garcia-Closas, Alina Vrieling, Graham G. Giles, Michael J. Kerin, Show Lin Yang, Nicola Miller, Sue Gerty, Thomas Brüning, Christopher A. Haiman, Kari Mononen, Loic Le Marchand, Jyh Cherng Yu, Anna Marie Mulligan, Jenny Chang-Claude, Christian R. Loehberg, Matthias W. Beckmann, Madeleine M.A. Tilanus-Linthorst, Angela Cox, Maartje J. Hooning, Susan E. Hankinson, Gianluca Severi, Angela M. Jones, Heli Nevanlinna, Caroline Weltens, Jolanta Lissowska, Hiltrud Brauch, Giu Cheng Hsu, Sebastian M. Jud, Per Hall, Hans Fischer, Arto Mannermaa, Christina Justenhoven, Laura Baglietto, Katri Pylkäs, Kristiina Aittomäki, Sara Margolin, T. Vandorpe, M. Barile, Ylermi Soini, Beate Pesch, Ellen L. Goode, Nayana Weerasooriya, Peter Devilee, Carl Blomqvist, Margriet Collée, Vesa Kataja, Arndt Hartmann, Manjeet K. Humphreys, Siranoush Manoukian, Annika Lindblom, Marjanka K. Schmidt, Yon Ko, Patrick Neven, Chia-Ni Hsiung, Xianshu Wang, Keith Humphreys, Dieter Flesch-Janys, Niall M. McInerney, Javier Benítez, Esther M. John, Jianjun Liu, Peter Sinn, Reijo Sironen, Annegien Broeks, Rebecca Hein, Shou Tung Chen, Paolo Radice, Simon S. Cross, Mark E. Sherman, Robert Paridaens, Shan Wang-Gohrke, Sebastian B. Weihbrecht, Jonine D. Figueroa, Catriona McLean, Georgia Chenevix-Trench, David J. Hunter, Henrik Flyger, Beata Peplonska, VU University medical center, EMGO - Quality of care, Virology, Medical Oncology, Clinical Genetics, Surgery, and University of Groningen
Subjects: Oncology, Cancer Research, Receptor, ErbB-2, Estrogen receptor, Body Mass Index, ErbB-2, 0302 clinical medicine, Risk Factors, Receptors, Odds Ratio, EPITHELIAL OVARIAN-CANCER, Progesterone, REPAIR GENES, 2. Zero hunger, 0303 health sciences, education.field_of_study, Tumor, Medicine (all), Age Factors, SINGLE-NUCLEOTIDE POLYMORPHISMS, Articles, 3. Good health, ErbB Receptors, Parity, ESTROGEN, Receptors, Estrogen, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Female, Breast disease, Receptors, Progesterone, Receptor, Receptor, erbB-2, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Oncology and Carcinogenesis, Population, Breast Neoplasms, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Biomarkers, Tumor, medicine, Humans, Oncology & Carcinogenesis, Obesity, Risk factor, education, 030304 developmental biology, Menarche, HORMONE-RECEPTOR, DIFFERENT HISTOPATHOLOGIC TYPES, Epidermal Growth Factor, business.industry, Parturition, Case-control study, Case-Control Studies, Keratin-5, Logistic Models, Receptor, Epidermal Growth Factor, Cancer, Odds ratio, BASAL-LIKE SUBTYPE, medicine.disease, Endocrinology, PROGESTERONE-RECEPTOR STATUS, business, Biomarkers
Abstract: BACKGROUND: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. METHODS: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. RESULTS: In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. CONCLUSIONS: This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.
Published: 2010
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22. Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls

Author: Amanda B. Spurdle, Manjeet K. Humphreys, Douglas F. Easton, Marjanka K. Schmidt, F.E. van Leeuwen, Letitia D. Smith, R.A.E.M. Tollenaar, Arto Mannermaa, Daehee Kang, Ian W. Brock, S. E. Bojesen, Jianjun Liu, Alfons Meindl, Melissa C. Southey, José Ignacio Arias, Louise A. Brinton, Jonathan Beesley, Keith Humphreys, Argyrios Ziogas, Jenny Chang-Claude, Laura Baglietto, I dos Santos Silva, G. Elliott, Caroline Seynaeve, Paul D.P. Pharoah, Antonenkova Nn, Peter Devilee, Janet E. Olson, Fergus J. Couch, Georgia Chenevix-Trench, Nicola F. Johnson, MW Reed, Ute Hamann, Vesa Kataja, Roger L. Milne, Nick Orr, Annegien Broeks, Sara Margolin, Dallas R. English, Natalia Bogdanova, Guillermo Pita, L.J. van 't Veer, Matthias W. Beckmann, Carl Blomqvist, M Garcia-Closas, Radka Platte, Keun-Young Yoo, Kristiina Aittomäki, H. Flyger, Dong-Young Noh, Reiner Strick, Iosif V. Zalutsky, Thilo Dörk, Alison M. Dunning, Peter Schürmann, Angela Cox, S. Chanock, Hiltrud Brauch, Melanie Maranian, Peter A. Fasching, Shahana Ahmed, Michael Bremer, Heli Nevanlinna, Tuomas Heikkinen, Kamila Czene, Jolanta Lissowska, Gianluca Severi, Claus R. Bartram, Regina Waltes, John L. Hopper, Zachary S. Fredericksen, Graham G. Giles, Arif B. Ekici, Yon-Dschun Ko, Annika Lindblom, Jonathan J. Morrison, Shan Wang-Gohrke, Rita K. Schmutzler, Julian Peto, Børge G. Nordestgaard, Barbara Burwinkel, Javier Benitez, Hoda Anton-Culver, Veli-Matti Kosma, Olivia Fletcher, Xianshu Wang, Per Hall, Alan Ashworth, C. J. van Asperen, Epidemiology and Data Science, EMGO - Quality of care, Hematology, Medical Oncology, and Clinical Genetics
Subjects: Oncology, medicine.medical_specialty, Genotype, Epidemiology, DNA Mutational Analysis, Mutation, Missense, Single-nucleotide polymorphism, Genome-wide association study, Breast Neoplasms, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Biology, Protein Serine-Threonine Kinases, Bioinformatics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Risk Factors, Internal medicine, medicine, Missense mutation, Humans, Genetic Predisposition to Disease, Polymorphism, 030304 developmental biology, 0303 health sciences, Case-Control Studies, DNA-Binding Proteins, Female, Protein-Serine-Threonine Kinases, Tumor Suppressor Proteins, Cancer, Single Nucleotide, medicine.disease, 3. Good health, Minor allele frequency, 030220 oncology & carcinogenesis, Mutation, Breast disease, Missense, genome-wide association ataxia-telangiectasia susceptibility alleles confer susceptibility truncating mutations common variants risk gene spectrum protein
Abstract: Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious. Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium. Results: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (Ptrend = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; Ptrend = 0.02). Conclusions: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer. Impact: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 19(9); 2143–51. ©2010 AACR.
Published: 2010
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23. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

Author: Eugenia E. Calle, Alice J. Sigurdson, Susan E. Hankinson, Alfons Meindl, Hoda Anton-Culver, Letitia D. Smith, Richard van Hien, R.A.E.M. Tollenaar, Louise A. Brinton, Veli-Matti Kosma, Stephen J. Chanock, Laura Baglietto, Anna González-Neira, Jonathan J. Morrison, Olivia Fletcher, Radka Platte, Michele M. Doody, Sei Hyun Ahn, Douglas F. Easton, Henrik Flyger, Merethe Kumle, Georgia Chenevix-Trench, Chen-Yang Shen, Beata Peplonska, Kamila Czene, J. David Curb, Christi J. van Asperen, Per Hall, Natalia Antonenkova, Irene L. Andrulis, Mieke Schutte, Claus R. Bartram, John L. Hopper, Daehee Kang, Amanda B. Spurdle, Peter Kraft, David J. Hunter, Kristiina Aittomäki, Bruce H. Alexander, Bruce A.J. Ponder, Malcolm W.R. Reed, Julia A. Knight, Christine D. Berg, Melissa C. Southey, S. A. Fedorova, Giu Cheng Hsu, Catherine A. McCarty, Arto Mannermaa, Rebecca Hein, Gianluca Severi, Peter Schürmann, Diana Eccles, Argyrios Ziogas, Shou Tung Chen, Ian W. Brock, Fergus J. Couch, Garnet L. Anderson, Ellen L. Goode, Nichola Johnson, Sara Margolin, Paul D.P. Pharoah, Annika Lindblom, W. Ryan Diver, Ute Hamann, Robert N. Hoover, Michael R. Stratton, Iosif V. Zalutsky, Yuqing Li, Sten Cornelissen, Natalia Bogdanova, Caroline Seynaeve, Rita K. Schmutzler, Julian Peto, Børge G. Nordestgaard, Robert Luben, Aleksandar Rajkovic, Stig E. Bojesen, Heather Spencer Feigelson, Saundra S. Buys, Marina Bermisheva, Barbara Burwinkel, Peter Devilee, Isabel dos Santos Silva, Jonathan Beesley, Thilo Dörk, Gilles Thomas, Lars J. Vatten, Tuomas Heikkinen, Ross L. Prentice, David G. Cox, D. Gareth Evans, Manjeet K. Humphreys, Marjanka K. Schmidt, Shan Wang-Gohrke, Melanie Maranian, Shahana Ahmed, Janet E. Olson, Dallas R. English, Maya Ghoussaini, Heli Nevanlinna, Dong Young Noh, Jolanta Lissowska, Graeme Elliott, Vesa Kataja, Nazneen Rahman, Peter Hillemanns, Annegien Broeks, Roger L. Milne, Johann H. Karstens, Christina Justenhoven, Montserrat Garcia-Closas, Karen A. Pooley, Zachary S. Fredericksen, Jyh Cherng Yu, Angela Cox, Maartje J. Hooning, Alison M. Dunning, Ans M.W. van den Ouweland, Hiltrud Brauch, Regina G. Ziegler, Jianjun Liu, Parveen Bhatti, Kristian Hveem, Kevin B. Jacobs, Catherine S. Healey, Jenny Chang-Claude, Michael J. Thun, Rogier A. Oldenburg, Elza Khusnutdinova, Xianshu Wang, Keun-Young Yoo, Carl Blomqvist, Gloria Ribas, Graham G. Giles, and Javier Benitez
Subjects: Genotype, Breast Neoplasms, Genome-wide association study, Biology, Article, Chromosomes, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Chromosome Mapping, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 3, Disease Susceptibility, Female, Genetic Predisposition to Disease, Genome, Human, Humans, Genetics, Genetic predisposition, medicine, 030304 developmental biology, Genetic association, 0303 health sciences, Genome, Pair 17, Cancer, medicine.disease, 3. Good health, TOX3, Pair 3, 030220 oncology & carcinogenesis, Breast disease, Human
Abstract: Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.
Published: 2009
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24. Risk of Estrogen Receptor-Positive and -Negative Breast Cancer and Single-Nucleotide Polymorphism 2q35-rs13387042

Author: Gianluca Severi, Hoda Anton-Culver, Veli-Matti Kosma, Peter Hillemanns, Louise A. Brinton, Douglas F. Easton, Georgia Chenevix-Trench, Roger L. Milne, Hui-Chun Wang, Chen-Yang Shen, Christie J. van Asperen, Hiltrud Brauch, M. Pilar Zamora, Rob A. E. M. Tollenaar, Heli Nevanlinna, Kristiina Aittomäki, Olivia Fletcher, Melissa C. Southey, Malcolm W.R. Reed, Jonathan Beesley, Jolanta Lissowska, Isabel dos Santos Silva, Nichola Johnson, Stig E. Bojesen, Per Hall, José Ignacio Arias, Tuomas Heikkinen, Janet E. Olson, Ian W. Brock, Clare Turnbull, Tatjana Nikolaeva, Dong-Young Noh, Yuqing Li, Paul D.P. Pharoah, Michael Bremer, Matthias W. Beckmann, Alison M. Dunning, Kamila Czene, Radka Platte, Keun-Young Yoo, Claus R. Bartram, Letitia D. Smith, John L. Hopper, kConFab Investigators, Natalia Antonenkova, Natalia Bogdanova, Stephen J. Chanock, Graeme Elliott, Vesa Kataja, Christina Justenhoven, Zachary S. Fredericksen, Thilo Dörk, Daehee Kang, Reiner Strick, Iosif V. Zalutsky, Shan Wang-Gohrke, Melanie Maranian, Shahana Ahmed, Peter Schürmann, Angela Cox, Arif B. Ekici, Sou-Tong Chen, Fergus J. Couch, Argyrios Ziogas, Jonathan J. Morrison, Jenny Chang-Claude, Yon-Dschun Ko, Henrik Flyger, Jianjun Liu, Peter A. Fasching, Caroline Seynaeve, Marina Bermisheva, Dallas R. English, Graham G. Giles, Xianshu Wang, Montserrat Garcia-Closas, Jyh-Cherng Yu, Nazneen Rahman, Elza Khusnutdinova, Rita K. Schmutzler, Julian Peto, Børge G. Nordestgaard, Carl Blomqvist, Barbara Burwinkel, Anthony Renwick, Manjeet K. Humphreys, Amanda B. Spurdle, Arto Mannermaa, Susanne Haas, Sarah Hines, Peter Devilee, Alfons Meindl, Laura Baglietto, Javier Benitez, Hematology, Medical Oncology, and Clinical Genetics
Subjects: Cancer Research, Estrogen receptor, Noninfiltrating, Linkage Disequilibrium, 0302 clinical medicine, Gene Frequency, Neoplasms, Ductal, Receptors, Odds Ratio, Breast, Progesterone, 0303 health sciences, Tumor, Medicine (all), Carcinoma, Ductal, Breast, Confounding Factors, Epidemiologic, Articles, Single Nucleotide, Middle Aged, Control subjects, Prognosis, 3. Good health, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, Female, Breast disease, Receptors, Progesterone, Adult, Asian Continental Ancestry Group, medicine.medical_specialty, Neoplasms, Hormone-Dependent, Genotype, Intraductal, European Continental Ancestry Group, Single-nucleotide polymorphism, Breast Neoplasms, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, Breast cancer, European origin, Asian People, SDG 3 - Good Health and Well-being, Predictive Value of Tests, Internal medicine, medicine, Biomarkers, Tumor, Confidence Intervals, Humans, Genetic Predisposition to Disease, Hormone-Dependent, Polymorphism, 030304 developmental biology, Aged, business.industry, Carcinoma, Odds ratio, medicine.disease, Carcinoma, Intraductal, Noninfiltrating, Case-Control Studies, Confounding Factors (Epidemiology), Estrogen, Endocrinology, Multicenter study, business, Humanities, Biomarkers
Abstract: Background: A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)–positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. Methods: 2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided. Results: We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; Ptrend = 1.0 x 10–19). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10–15) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)–positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10–14) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002). Conclusion: The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women. Roger L. Milne, Javier Benitez, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomaki, Carl Blomqvist, Jose Ignacio Arias, M. Pilar Zamora, Barbara Burwinkel, Claus R. Bartram, Alfons Meindl, Rita K. Schmutzler, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W. R. Reed, Melissa C. Southey, Letitia Smith, Amanda B. Spurdle, John L. Hopper, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Peter Schurmann, Michael Bremer, Peter Hillemanns, Thilo Dork, Peter Devilee, Christie J. van Asperen, Rob A. E. M. Tollenaar, Caroline Seynaeve, Per Hall, Kamila Czene, Jianjun Liu, Yuqing Li, Shahana Ahmed, Alison M. Dunning, Melanie Maranian, Paul D. P. Pharoah, Georgia Chenevix-Trench, Jonathan Beesley, kConFab Investigators,, AOCS Group, Natalia V. Bogdanova, Natalia N. Antonenkova, Iosif V. Zalutsky, Hoda Anton-Culver, Argyrios Ziogas, Hiltrud Brauch, Christina Justenhoven, Yon-Dschun Ko, Susanne Haas, Peter A. Fasching, Reiner Strick, Arif B. Ekici, Matthias W. Beckmann, Graham G. Giles, Gianluca Severi, Laura Baglietto, Dallas R. English, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Clare Turnbull, Sarah Hines, Anthony Renwick, Nazneen Rahman, Borge G. Nordestgaard, Stig E. Bojesen, Henrik Flyger, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Montserrat Garcia-Closas, Stephen Chanock, Jolanta Lissowska, Louise A. Brinton, Jenny Chang-Claude, Shan Wang-Gohrke, Chen-Yang Shen, Hui-Chun Wang, Jyh-Cherng Yu, Sou-Tong Chen, Marina Bermisheva, Tatjana Nikolaeva, Elza Khusnutdinova, Manjeet K. Humphreys, Jonathan Morrison, Radka Platte, Douglas F. Easton, on behalf of the Breast Cancer Association Consortium
Published: 2009

25. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

Author: Melissa C. Southey, Nils Schoof, Per Hall, Mitul Shah, Helena Kemiläinen, Matthias W. Beckmann, Mia M. Gaudet, Paul D.P. Pharoah, Alina Vrieling, Dominiek Smeets, Alexander Miron, Amanda B. Spurdle, Florence Menegaux, Lorna Gibson, Pascal Guénel, Jonine D. Figueroa, Julia A. Knight, Manjeet K. Humphreys, H. B. Christina Justenhoven, Marjanka K. Schmidt, Hoda Anton-Culver, Veli-Matti Kosma, B. Pesch, Elizabeth K. Cahoon, Peter A. Fasching, Anja Rudolph, Dieter Flesch-Janys, Robert Paridaens, Anna deFazio, Amy Trentham-Dietz, Thérèse Truong, Anna Marie Mulligan, Arto Mannermaa, Celine M. Vachon, Diether Lambrechts, Gianluca Severi, Alison M. Dunning, Sabapathy P. Balasubramanian, Shan Wang-Gohrke, Julian Peto, Olivia Fletcher, Polly A. Newcomb, Børge G. Nordestgaard, Stephen J. Chanock, Dorota M. Gertig, Kristen N. Stevens, Jianjun Liu, Graham G. Giles, Penny Webb, Linda J. Titus, Heather Thorne, Esther M. John, Georgia Chenevix-Trench, Doug Easton, Kenneth Offit, Isabel dos Santos Silva, Gord Glendon, Sabine Behrens, Eveline Niedermayr, Argyrios Ziogas, Charlotte Lanng, Janet E. Olson, Hans-Peter Fischer, Eija Myöhänen, Emilie Cordina-Duverger, Laura Baglietto, Anne Lotz, Hiltrud Brauch, A. Green, David D.L. Bowtell, Stefan Nickels, Jaana M. Hartikainen, Roger L. Milne, Montserrat Garcia-Closas, Katharina Buck, Helen Cramp, Vesa Kataja, Thomas Brüning, Christina A. Clarke, Dan Connley, Arif B. Ekici, Heiko Müller, John L. Hopper, Yon-Dschun Ko, Leslie Bernstein, Preetha Rajaraman, Martina E. Schmidt, Michele M. Doody, Alice J. Sigurdson, Irene L. Andrulis, Volker Harth, Enes Makalic, Sylvia Rabstein, Lothar Häberle, Fergus J. Couch, Christian Baisch, Ute Hamann, Hermann Brenner, Patrick Neven, Rebecca Hein, Daniel F. Schmidt, Kathleen Egan, Christa Stegmaier, Jolanta Lissowska, Angela Cox, Jean S Wang, Volker Arndt, Ursula Eilber, Stig E. Bojesen, Jenny Chang-Claude, and Nadia Obi
Subjects: Cancer Research, Genotype, Evolution, European Continental Ancestry Group, Breast Neoplasms, QH426-470, Biology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Behavior and Systematics, Risk Factors, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Polymorphism, Gene–environment interaction, Molecular Biology, Alleles, Genetic Association Studies, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 2. Zero hunger, Caspase 8, 0303 health sciences, Ecology, Microfilament Proteins, Cancer, Single Nucleotide, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Female, Polymorphism, Single Nucleotide, Gene-Environment Interaction, 030220 oncology & carcinogenesis, Relative risk, Menarche, Body mass index, Demography
Abstract: Contains fulltext : 118401.pdf (Publisher’s version ) (Open Access) Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 x 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 x 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of /= 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 x 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.
Published: 2013

26. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

Author: Stefan, Nickels, Thérèse, Truong, Rebecca, Hein, Kristen, Stevens, Katharina, Buck, Sabine, Behrens, Ursula, Eilber, Martina, Schmidt, Lothar, Häberle, Alina, Vrieling, Mia, Gaudet, Jonine, Figueroa, Nils, Schoof, Amanda B, Spurdle, Anja, Rudolph, Peter A, Fasching, John L, Hopper, Enes, Makalic, Daniel F, Schmidt, Melissa C, Southey, Matthias W, Beckmann, Arif B, Ekici, Olivia, Fletcher, Lorna, Gibson, Isabel dos Santos, Silva, Julian, Peto, Manjeet K, Humphreys, Jean, Wang, Emilie, Cordina-Duverger, Florence, Menegaux, Børge G, Nordestgaard, Stig E, Bojesen, Charlotte, Lanng, Hoda, Anton-Culver, Argyrios, Ziogas, Leslie, Bernstein, Christina A, Clarke, Hermann, Brenner, Heiko, Müller, Volker, Arndt, Christa, Stegmaier, Hiltrud, Brauch, Thomas, Brüning, Volker, Harth, Arto, Mannermaa, Vesa, Kataja, Veli-Matti, Kosma, Jaana M, Hartikainen, Diether, Lambrechts, Dominiek, Smeets, Patrick, Neven, Robert, Paridaens, Dieter, Flesch-Janys, Nadia, Obi, Shan, Wang-Gohrke, Fergus J, Couch, Janet E, Olson, Celine M, Vachon, Graham G, Giles, Gianluca, Severi, Laura, Baglietto, Kenneth, Offit, Esther M, John, Alexander, Miron, Irene L, Andrulis, Julia A, Knight, Gord, Glendon, Anna Marie, Mulligan, Stephen J, Chanock, Jolanta, Lissowska, Jianjun, Liu, Angela, Cox, Helen, Cramp, Dan, Connley, Sabapathy, Balasubramanian, Alison M, Dunning, Mitul, Shah, Amy, Trentham-Dietz, Polly, Newcomb, Linda, Titus, Kathleen, Egan, Elizabeth K, Cahoon, Preetha, Rajaraman, Alice J, Sigurdson, Michele M, Doody, Pascal, Guénel, Paul D P, Pharoah, Marjanka K, Schmidt, Per, Hall, Doug F, Easton, Montserrat, Garcia-Closas, Roger L, Milne, and Jenny, Chang-Claude
Subjects: Caspase 8, Genotype, Epidemiology, Microfilament Proteins, Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, White People, Risk Factors, Genetic Epidemiology, Humans, Medicine, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Cancer Epidemiology, Research Article
Abstract: Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene–environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10−6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10−4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01–1.16) in nulliparous women and ranged from 1.03 (0.96–1.10) in parous women with one birth to 1.26 (1.16–1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85–0.98) in those with an alcohol intake of, Author Summary Breast cancer involves combined effects of numerous genetic, environmental, and behavioral risk factors that are unique to each individual. High risk genes, such as BRCA1 and BRCA2, account for only a small proportion of disease occurrence. Recent genome-wide research has identified more than 20 common genetic variants, which individually alter breast cancer risk very moderately. We undertook an international collaborative study to determine whether the effect of these genetic variants vary with environmental factors, such as parity, body mass index (BMI), height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, and physical activity, which are known to affect risk of developing breast cancer. Using pooled data from 24 studies of the Breast Cancer Association Consortium (BCAC), we provide first convincing evidence that the breast cancer risk associated with a genetic variant in LSP1 differs with the number of births and that the risk associated with a CASP8 variant is altered by high alcohol consumption. The effect of an additional genetic variant might also be modified by reproductive factors. This knowledge will stimulate new research towards a better understanding of breast cancer development.
Published: 2012

27. Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors

Author: Mia M, Gaudet, Karoline B, Kuchenbaecker, Joseph, Vijai, Robert J, Klein, Tomas, Kirchhoff, Lesley, McGuffog, Daniel, Barrowdale, Alison M, Dunning, Andrew, Lee, Joe, Dennis, Sue, Healey, Ed, Dicks, Penny, Soucy, Olga M, Sinilnikova, Vernon S, Pankratz, Xianshu, Wang, Ronald C, Eldridge, Daniel C, Tessier, Daniel, Vincent, Francois, Bacot, Frans B L, Hogervorst, Susan, Peock, Dominique, Stoppa-Lyonnet, Paolo, Peterlongo, Rita K, Schmutzler, Katherine L, Nathanson, Marion, Piedmonte, Christian F, Singer, Mads, Thomassen, Thomas v O, Hansen, Susan L, Neuhausen, Ignacio, Blanco, Mark H, Greene, Judith, Garber, Jeffrey N, Weitzel, Irene L, Andrulis, David E, Goldgar, Emma, D'Andrea, Trinidad, Caldes, Heli, Nevanlinna, Ana, Osorio, Elizabeth J, van Rensburg, Adalgeir, Arason, Gad, Rennert, Ans M W, van den Ouweland, Annemarie H, van der Hout, Carolien M, Kets, Cora M, Aalfs, Juul T, Wijnen, Margreet G E M, Ausems, Debra, Frost, Steve, Ellis, Elena, Fineberg, Radka, Platte, D Gareth, Evans, Chris, Jacobs, Julian, Adlard, Marc, Tischkowitz, Mary E, Porteous, Francesca, Damiola, Lisa, Golmard, Laure, Barjhoux, Michel, Longy, Muriel, Belotti, Sandra Fert, Ferrer, Sylvie, Mazoyer, Amanda B, Spurdle, Siranoush, Manoukian, Monica, Barile, Maurizio, Genuardi, Norbert, Arnold, Alfons, Meindl, Christian, Sutter, Barbara, Wappenschmidt, Susan M, Domchek, Georg, Pfeiler, Eitan, Friedman, Uffe Birk, Jensen, Mark, Robson, Sohela, Shah, Conxi, Lazaro, Phuong L, Mai, Javier, Benitez, Melissa C, Southey, Marjanka K, Schmidt, Peter A, Fasching, Julian, Peto, Manjeet K, Humphreys, Qin, Wang, Kyriaki, Michailidou, Elinor J, Sawyer, Barbara, Burwinkel, Pascal, Guénel, Stig E, Bojesen, Roger L, Milne, Hermann, Brenner, Magdalena, Lochmann, Kristiina, Aittomäki, Thilo, Dörk, Sara, Margolin, Arto, Mannermaa, Diether, Lambrechts, Jenny, Chang-Claude, Paolo, Radice, Graham G, Giles, Christopher A, Haiman, Robert, Winqvist, Peter, Devillee, Montserrat, García-Closas, Nils, Schoof, Maartje J, Hooning, Angela, Cox, Paul D P, Pharoah, Anna, Jakubowska, Nick, Orr, Anna, González-Neira, Guillermo, Pita, M Rosario, Alonso, Per, Hall, Fergus J, Couch, Jacques, Simard, David, Altshuler, Douglas F, Easton, Georgia, Chenevix-Trench, Antonis C, Antoniou, and Kenneth, Offit
Subjects: Adult, BRCA2 Protein, Heterozygote, Genotype, BRCA1 Protein, Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Mutation, Genetics, Cancer Genetics, Genome-Wide Association Studies, Humans, Chromosomes, Human, Pair 6, Female, Genetic Predisposition to Disease, skin and connective tissue diseases, Biology, Alleles, Aged, Genome-Wide Association Study, Research Article
Abstract: Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80–0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer., Author Summary Women who carry BRCA2 mutations have an increased risk of breast cancer that varies widely. To identify common genetic variants that modify the breast cancer risk associated with BRCA2 mutations, we have built upon our previous work in which we examined genetic variants across the genome in relation to breast cancer risk among BRCA2 mutation carriers. Using a custom genotyping platform with 211,155 genetic variants known as single nucleotide polymorphisms (SNPs), we genotyped 3,881 women who had breast cancer and 4,330 women without breast cancer, which represents the largest possible, international collection of BRCA2 mutation carriers. We identified that a SNP located at 6p24 in the genome was associated with lower risk of breast cancer. Importantly, this SNP was not associated with breast cancer in BRCA1 mutation carriers or in a general population of women, indicating that the breast cancer association with this SNP might be specific to BRCA2 mutation carriers. Combining this BRCA2-specific SNP with 13 other breast cancer risk SNPs also known to modify risk in BRCA2 mutation carriers, we were able to derive a risk prediction model that could be useful in helping women with BRCA2 mutations weigh their risk-reduction strategy options.
Published: 2012

28. Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

Author: Peter Hillemanns, Roger L. Milne, Chiun-Sheng Huang, Jan Lubinski, Arif B. Ekici, Rita K. Schmutzler, Julian Peto, Qin Wang, Rob A. E. M. Tollenaar, Børge G. Nordestgaard, Chen-Yang Shen, Paolo Radice, Nicola Miller, Barbara Burwinkel, Suleeporn Sangrajrang, Núria Malats, James McKay, Gianluca Severi, Ian Tomlinson, Dong-Young Noh, Irene L. Andrulis, Xiaoqing Chen, Esther M. John, Katarzyna Durda, Anna Marie Mulligan, Anne Lise Børrensen-Dale, Frederik Marmé, Simon S. Cross, Elza Khusnutdinova, Joerg Heil, Gillian S. Dite, Melissa C. Southey, Thilo Dörk, Peter Kraft, Monica Barile, Graeme Elliot, Olivia Fletcher, Yuri I. Rogov, Arto Mannermaa, Nazneen Rahman, Annegien Broeks, Susan E. Hankinson, Xianshu Wang, Natalia Bogdanova, Mark E. Sherman, Volker Harth, Johann H. Karstens, Montserrat Garcia-Closas, Robert Winqvist, Alfons Meindl, Rebecca Hein, Laura J. van't Veer, Stefan Nickels, Manjeet K. Humphreys, Valerie Gaborieau, Lorna Gibson, Jose Ignacio Arias Perez, Giuseppe Floris, Christa Stegmaier, Gord Glendon, Heiko Müller, Marjanka K. Schmidt, Jonine D. Figueroa, Julia A. Knight, Graham G. Giles, Siranoush Manoukian, Ming-Feng Hou, Albina Farahtdinova, Gilles Thomas, Diether Lambrechts, Anna Jakubowska, Paul D.P. Pharoah, Alexander Miron, Michael J. Kerin, Iosif V. Zalutsky, Ian W. Brock, Laura Baglietto, Argyrios Ziogas, Claus R. Bartram, John L. Hopper, Marina Bermisheva, Grethe I. Grenaker Alnæs, Jaana M. Hartikainen, Sei Hyun Ahn, Hermann Brenner, Paul Brennan, Dieter Flesch-Janys, Stephen J. Chanock, Robert N. Hoover, Fergus J. Couch, Georgia Chenevix-Trench, Anthony Renwick, Sheila Seal, Mervi Grip, Matthias W. Beckmann, Karin Leunen, Javier Benitez, Peter Schürmann, Vesa Kataja, Arja Jukkola-Vuorinen, Peter A. Fasching, David J. Hunter, Christian M. Bayer, Rogier A. Oldenburg, Karen A. Pooley, Antoinette Hollestelle, Hoda Anton-Culver, Veli-Matti Kosma, P. Zamora, Jonathan Beesley, Paolo Peterlongo, Darya Prokofieva, Keun-Young Yoo, Isabel dos Santos Silva, Katarzyna Jaworska, Janet E. Olson, Carmel Apicella, U Hamann, Jyh-Cherng Yu, Shan Wang-Gohrke, Natalia Antonenkova, Sara Lindström, Andreas Schneeweiss, Katri Pylkäs, Douglas F. Easton, Charlotte Lanng, Alison M. Dunning, Vessela N. Kristensen, Daehee Kang, Elinor J. Sawyer, Jolanta Lissowska, Christina Justenhoven, Zachary S. Fredericksen, Madeleine M.A. Tilanus-Linthorst, Angela Cox, Maartje J. Hooning, Volker Arndt, Christof Sohn, Betül T. Yesilyurt, Jenny Chang-Claude, Ellen L. Goode, Stig E. Bojesen, Clare Turnbull, Medical Oncology, Clinical Genetics, and Surgery
Subjects: Oncology, Epidemiology, Estrogen receptor, Noninfiltrating, Cohort Studies, 0302 clinical medicine, Risk Factors, Ductal, Receptors, common variants, Breast, Progesterone, risk, 0303 health sciences, subtypes, Carcinoma, Ductal, Breast, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Case-Control Studies, Chromosomes, Human, Pair 5, Female, Follow-Up Studies, Humans, Neoplasm Grading, Polymorphism, Single Nucleotide, Prognosis, Receptors, Estrogen, Receptors, Progesterone, Genetic Predisposition to Disease, Single Nucleotide, 3. Good health, 030220 oncology & carcinogenesis, alleles, Pair 5, Human, medicine.medical_specialty, Intraductal, Biology, Article, Chromosomes, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Progesterone receptor, medicine, Genetic predisposition, Carcinoma, Polymorphism, 030304 developmental biology, Gynecology, Case-control study, Ductal carcinoma, confer susceptibility, medicine.disease, Estrogen, genome-wide association, Histopathology
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; Pheterogeneity = 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. Cancer Epidemiol Biomarkers Prev; 20(10); 2222–31. ©2011 AACR.
Published: 2011
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29. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

Author: Graham G. Giles, Sandrine Tchatchou, Bart Claes, Fergus J. Couch, Douglas F. Easton, Simon S. Cross, Manjeet K. Humphreys, Irene L. Andrulis, Annika Lindblom, Paul Brennan, Bahar Ozturk, Marjanka K. Schmidt, Ute Hamann, Carlos Caldas, Thomas Löning, Alexander Hein, Peter Hillemanns, Roger L. Milne, Matti Eskelinen, Melissa C. Southey, Patrick Neven, Rob A. E. M. Tollenaar, Giu-Cheng Hsu, Päivi Heikkilä, Jonathan Beesley, Keith Humphreys, Malcolm W.R. Reed, Hiltrud Brauch, Valerie Gaborieau, Laurence N. Kolonel, Alison M. Dunning, Sabapathy P. Balasubramanian, Jianjun Liu, Diljit Kaur-Knudsen, Anna Jakubowska, Paul D.P. Pharoah, Geert J.L.H. van Leenders, Matthew L. Kosel, Angela Cox, Christopher A. Haiman, Aocs, Arif B. Ekici, Peter A. Fasching, Ruediger Schulz-Wendtland, Anne Lise Børresen-Dale, Loic Le Marchand, Maartje J. Hooning, Fleur Hammet, Christof Sohn, Gillian S. Dite, Yon-Dschun Ko, Sebastian M. Jud, Per Hall, Mark E. Sherman, Jaana M. Kauppinen, Bohdan Górski, Dieter Flesch-Janys, Fiona M. Blows, Sara Margolin, Jacek Gronwald, Jonine D. Figueroa, Amanda B. Spurdle, Thilo Dörk, Javier Benitez, Catriona McLean, Chia-Ni Hsiung, Matthias W. Beckmann, Ylermi Soini, kConFab, Frederik Marmé, Georgia Chenevix-Trench, David Dynnes Ørsted, Johann H. Karstens, Hoda Anton-Culver, Veli-Matti Kosma, Christi J. van Asperen, Montserrat Garcia-Closas, Annegien Broeks, Arto Mannermaa, Thomas Brüning, Jenny Chang-Claude, Xiaoqing Chen, Päivi Auvinen, Carl Blomqvist, David J. Hunter, Anna Marie Mulligan, Kristiina Aittomäki, Michael Bremer, Renate de Groot, Shou-Tung Chen, Kirsimari Aaltonen, Beate Pesch, Helene Holland, Susan E. Hankinson, Kamila Czene, Jan Lubinski, Mieke Kriege, Ming-Feng Hou, Vesa Kataja, John L. Hopper, Diether Lambrechts, Carmel Apicella, Petra E A Huijts, Brian E. Henderson, Laura Baglietto, Rebecca Hein, Helen Cramp, Frances P. O'Malley, Arndt Hartmann, Grethe I. Grenaker Alnæs, Louise A. Brinton, Jyh-Cherng Yu, Primitiva Menéndez Rodríguez, T. Vandorpe, Elena Provenzano, Peter Devilee, Tomasz Byrski, Heli Nevanlinna, Stig E. Bojesen, Tuomas Heikkinen, Jolanta Lissowska, Beata Peplonska, Argyrios Ziogas, Christina Justenhoven, Tomasz Huzarski, Zachary S. Fredericksen, Agnes Jager, Caroline Seynaeve, Chiun-Sheng Huang, Vessela N. Kristensen, Daniel Connley, Børge G. Nordestgaard, Barbara Burwinkel, Vincent T.H.B.M. Smit, Kristy Driver, Antoinette Hollestelle, Letitia D. Smith, Stephen J. Chanock, Hans-Peter Sinn, Chen-Yang Shen, Suleeporn Sangrajrang, Andreas Schneeweiss, Rogier A. Oldenburg, Jose Ignacio Arias Perez, Xiaohong R. Yang, Henrik Flyger, Hans-Peter Fischer, Pilar Zamora, Laura J. van't Veer, Xianshu Wang, Cezary Cybulski, Hans Wildiers, Shan Wang-Gohrke, Gianluca Severi, Medical Oncology, Clinical Genetics, and Pathology
Subjects: Oncology, Candidate gene, Receptor, ErbB-2, Estrogen receptor, Genome-wide association study, Penetrance, Bioinformatics, 0302 clinical medicine, ErbB-2, Risk Factors, Receptors, Odds Ratio, Asian Continental Ancestry Group, Biomarkers, Tumor, Breast Neoplasms, European Continental Ancestry Group, Female, Genetic Loci, Humans, Receptors, Estrogen, Receptors, Progesterone, Genetic Predisposition to Disease, Molecular Biology, Genetics, Genetics (clinical), Progesterone, 0303 health sciences, education.field_of_study, Tumor, Association Studies Articles, General Medicine, 3. Good health, Risk factors for breast cancer, 030220 oncology & carcinogenesis, Receptor, medicine.medical_specialty, Population, Biology, Auto-immunity, transplantation and immunotherapy [N4i 4], White People, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Asian People, Internal medicine, medicine, education, 030304 developmental biology, medicine.disease, Estrogen, TOX3, Biomarkers
Abstract: Contains fulltext : 96071.pdf (Publisher’s version ) (Closed access) Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 x 10(-18)), rs3803662 (16q12) (P = 3.7 x 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 x 10(-6) and P = 4.1 x 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P
Published: 2011

30. TGF-β signalling pathway and breast cancer susceptibility

Author: Robin Hesketh, Caroline Baynes, Douglas F. Easton, Jolanta Lissowska, Craig Luccarini, Paul D.P. Pharoah, Alison M. Dunning, Manjeet K. Humphreys, Serena Scollen, Kristy Driver, Jonine D. Figueroa, Montserrat Garcia-Closas, and James C. Metcalfe
Subjects: medicine.medical_specialty, Epidemiology, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Transforming Growth Factor beta, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Prospective Studies, 030304 developmental biology, Aged, Neoplasm Staging, 0303 health sciences, Cancer, ACVRL1, Endoglin, Middle Aged, medicine.disease, Prognosis, Primary tumor, 3. Good health, Minor allele frequency, Endocrinology, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Cancer research, Female, Breast disease, Disease Susceptibility, Signal Transduction
Abstract: Background: TGF-β acts as a suppressor of primary tumor initiation but has been implicated as a promoter of the later malignant stages. Here associations with risk of invasive breast cancer are assessed for single-nucleotide polymorphisms (SNP) tagging 17 genes in the canonical TGF-β ALK5/SMADs 2&3 and ALK1/SMADs 1&5 signaling pathways: LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, and SMAD7 [Approved Human Gene Nomenclature Committee gene names: ACVRL1 (for ALK1) and ENG (for Endoglin)]. Methods: Three-hundred-fifty-four tag SNPs (minor allele frequency > 0.05) were selected for genotyping in a staged study design using 6,703 cases and 6,840 controls from the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) study. Significant associations were meta-analyzed with data from the NCI Polish Breast Cancer Study (PBCS; 1,966 cases and 2,347 controls) and published data from the Breast Cancer Association Consortium (BCAC). Results: Associations of three SNPs, tagging TGFB1 (rs1982073), TGFBR1 (rs10512263), and TGFBR2 (rs4522809), were detected in SEARCH; however, associations became weaker in meta-analyses including data from PBCS and BCAC. Tumor subtype analyses indicated that the TGFB1 rs1982073 association may be confined to increased risk of developing progesterone receptor negative (PR−) tumors [1.18 (95% CI: 1.09–1.28), 4.1 × 10−5 (P value for heterogeneity of ORs by PR status = 2.3 × 10−4)]. There was no evidence for breast cancer risk associations with SNPs in the endothelial-specific pathway utilizing ALK1/SMADs 1&5 that promotes angiogenesis. Conclusion: Common variation in the TGF-β ALK5/SMADs 2&3 signaling pathway, which initiates signaling at the cell surface to inhibit cell proliferation, might be related to risk of specific tumor subtypes. Impact: The subtype specific associations require very large studies to be confirmed. Cancer Epidemiol Biomarkers Prev; 20(6); 1112–9. ©2011 AACR.
Published: 2011

31. Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk

Author: Celine M. Vachon, Irene L. Andrulis, Peter Schürmann, Arja Jukkola-Vuorinen, Manjeet K. Humphreys, Lorna Gibson, Natalia Bogdanova, Jean Wang, Annika Lindblom, Marjanka K. Schmidt, Annegien Broeks, Ian W. Brock, A. Miron, Janet E. Olson, James McKay, Michael J. Kerin, Gilles Thomas, Anna González-Neira, Ian Tomlinson, Jaana M. Hartikainen, Anna Marie Mulligan, P. A. Fasching, Gillian S. Dite, I dos Santos Silva, Keun-Young Yoo, Rebecca Hein, Michael Bremer, Thilo Dörk, Ji Arias Pérez, C. R. Bartrar, Sara Margolin, Javier Benitez, Jo Knight, Suleeporn Sangrajrang, Alison M. Dunning, Matthias W. Beckmann, Rita K. Schmutzler, Julian Peto, John L. Hopper, Natalia Antonenkova, Angela Cox, Yuri I. Rogov, Barbara Burwinkel, Robert N. Hoover, L.J. van 't Veer, Nicola F. Johnson, Fergus J. Couch, Jenny Chang-Claude, Arto Mannermaa, Ute Hamann, Hoda Anton-Culver, Douglas F. Easton, Jolanta Lissowska, Graeme Elliott, Vesa Kataja, Montserrat Garcia-Closas, Elinor J. Sawyer, Alfons Meindl, Kristen N. Stevens, Peter Hillemanns, Veli-Matti Kosma, R.A.E.M. Tollenaar, Thomas Brüning, Stephen J. Chanock, Zachary S. Fredericksen, Carmel Apicella, Laura Baglietto, Mervi Grip, Roger L. Milne, James R. Cerhan, Karen A. Pooley, Paolo Peterlongo, Matthew L. Kosel, Daehee Kang, Argyrios Ziogas, Arif B. Ekici, Yon-Dschun Ko, Shan Wang-Gohrke, Graham G. Giles, Alexander Hein, Xianshu Wang, Bernardo Bonanni, Gianluca Severi, Loris Bernard, P Pharoah, Dong-Young Noh, Xiaoqing Chen, Esther M. John, Melissa C. Southey, K. Pylkäs, Robert Winqvist, Vernon S. Pankratz, Catriona McLean, Georgia Chenevix-Trench, J. V. Zalutsky, David J. Hunter, Siranoush Manoukian, Simon S. Cross, Gordon Glendon, V. Gabrieau, and Paul Brennan
Subjects: Oncology, poor-prognosis, medicine.medical_specialty, Cancer Research, Class I Phosphatidylinositol 3-Kinases, Breast Neoplasms, Biology, Germline, 03 medical and health sciences, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Breast cancer, Polymorphism (computer science), Internal medicine, Neoplasms, medicine, Genetic predisposition, Genetic susceptibility, ovarian, Humans, Genetic Predisposition to Disease, gene, 030304 developmental biology, 0303 health sciences, pten loss, Oncogene, pathway, Case-control study, pik3ca mutations, association, Cancer, Genetic Variation, Genetics and Genomics, Odds ratio, correlate, medicine.disease, 3. Good health, Association study, high-frequency, 030220 oncology & carcinogenesis, Case-Control Studies, Immunology, Female
Abstract: BACKGROUND: Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer. METHODS: A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC). RESULTS: Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR) = 0.97, 95% confidence interval (CI) 0.95-0.99, P = 4.6 x 10(-3)), but did not reach significance in the BCAC replication study alone (OR = 0.98, 95% CI 0.96-1.01, P = 0.139). CONCLUSION: Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer British Journal of Cancer (2011) 105, 1934 - 1939. doi: 10.1038/bjc.2011.448 www.bjcancer.com Published online 27 October 2011 (C) 2011 Cancer Research UK
Published: 2011

32. Prognostic Significance of Subtype Classification for Short- and Long-Term Survival in Breast Cancer: Survival Time Holds the Key

Author: Manjeet K. Humphreys, Marjanka K. Schmidt, Fergus J. Couch, Elena Provenzano, Douglas F. Easton, Vicky Cafourek, Jelle Wesseling, Maggie C.U. Cheang, Flora E. van Leeuwen, Karen A. Gelmon, Malcolm W.R. Reed, Torsten O. Nielsen, Alison M. Dunning, Gianluca Severi, Emad A. Rakha, Fiona M. Blows, Montserrat Garcia-Closas, Laura Baglietto, Janet E. Olson, Annegien Broeks, Sarah-Jane Dawson, David G. Huntsman, Carl Blomqvist, William F. Anderson, Catriona McLean, William D. Foulkes, Kristy Driver, Graham G. Giles, Louis R. Bégin, Carlos Caldas, Lars A. Akslen, Simon S. Cross, Ian O. Ellis, Päivi Heikkilä, Mark E. Sherman, Andrew R. Green, Xianshu Wang, Heli Nevanlinna, Jolanta Lissowska, Angela Cox, Melissa C. Southey, Paul D.P. Pharoah, Tuomas Heikkinen, Department of Oncology, Department of Pathology, Department of Obstetrics and Gynecology, Women's Health Research Program, Epidemiology and Data Science, and EMGO - Quality of care
Subjects: Oncology, Pathology, Time Factors, 312 Clinical medicine, PHENOTYPE, Biochemistry, Basal (phylogenetics), 0302 clinical medicine, Receptors, 80 and over, Epidermal growth factor receptor, Young adult, RISK, Aged, 80 and over, 0303 health sciences, Tumor, biology, General Medicine, ASSOCIATION, CHEMOTHERAPY, Middle Aged, Prognosis, Immunohistochemistry, 3. Good health, ErbB Receptors, Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716 [VDP], TUMOR CHARACTERISTICS, PREMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, CARCINOMAS, Oncology/Breast Cancer, Perspective, Cell Surface, Hormonal therapy, Medicine, Keratins, Female, Research Article, Receptor, Biotechnology, EXPRESSION, Adult, medicine.medical_specialty, education, Receptors, Cell Surface, Breast Neoplasms, Aged, Biomarkers, Tumor, Hormones, Humans, Proportional Hazards Models, Receptor, Epidermal Growth Factor, Young Adult, Molecular Biology, Cell Biology, 03 medical and health sciences, Cytokeratin, Breast cancer, Internal medicine, medicine, Adjuvant therapy, POLYMORPHISMS, 030304 developmental biology, Epidermal Growth Factor, Proportional hazards model, medicine.disease, GENE, biology.protein, Biomarkers
Abstract: Paul Pharoah and colleagues evaluate the prognostic significance of immunohistochemical subtype classification in more than 10,000 breast cancer cases with early disease, and examine the influence of a patient's survival time on the prediction of future survival., Background Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype. Methods and Findings We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data. Tumours were classified as luminal and nonluminal tumours according to hormone receptor expression. These two groups were further subdivided according to expression of HER2, and finally, the luminal and nonluminal HER2-negative tumours were categorised according to expression of basal markers. Changes in mortality rates over time differed by subtype. In women with luminal HER2-negative subtypes, mortality rates were constant over time, whereas mortality rates associated with the luminal HER2-positive and nonluminal subtypes tended to peak within 5 y of diagnosis and then decline over time. In the first 5 y after diagnosis the nonluminal tumours were associated with a poorer prognosis, but over longer follow-up times the prognosis was poorer in the luminal subtypes, with the worst prognosis at 15 y being in the luminal HER2-positive tumours. Basal marker expression distinguished the HER2-negative luminal and nonluminal tumours into different subtypes. These patterns were independent of any systemic adjuvant therapy. Conclusions The six subtypes of breast cancer defined by expression of five markers show distinct behaviours with important differences in short term and long term prognosis. Application of these markers in the clinical setting could have the potential to improve the targeting of adjuvant chemotherapy to those most likely to benefit. The different patterns of mortality over time also suggest important biological differences between the subtypes that may result in differences in response to specific therapies, and that stratification of breast cancers by clinically relevant subtypes in clinical trials is urgently required. Please see later in the article for the Editors' Summary, Editors' Summary Background Each year, more than one million women discover they have breast cancer. Breast cancer begins when cells in the breast's milk-producing glands or in the tubes (ducts) that take milk to the nipples acquire genetic changes that allow them to divide uncontrollably and to move around the body (metastasize). The uncontrolled cell division leads to the formation of a lump that can be detected by mammography (a breast X-ray) or by manual breast examination. Breast cancer is treated by surgical removal of the lump or, if the cancer has started to spread, by removal of the whole breast (mastectomy). Surgery is usually followed by radiotherapy or chemotherapy. These “adjuvant” therapies are designed to kill any remaining cancer cells but can make women very ill. Generally speaking, the outlook (prognosis) for women with breast cancer is good. In the United States, for example, nearly 90% of affected women are still alive five years after their diagnosis. Why Was This Study Done? Because there are several types of cells in the milk ducts and glands, there are several subtypes of breast cancer. Luminal tumors, for example, begin in the cells that line the ducts and glands and usually grow slowly; basal-type tumors arise in deeper layers of the ducts and glands and tend to grow quickly. Clinicians need to distinguish between different breast cancer subtypes so that they can give women a realistic prognosis and can give adjuvant treatments to those women who are most likely to benefit. One way to distinguish between different subtypes is to stain breast cancer samples using antibodies (immune system proteins) that recognize particular proteins (antigens). This “immunohistochemical” approach can identify several breast cancer subtypes but its prognostic value and the best way to classify breast tumors remains unclear. In this study, the researchers investigate the survival over time of women with six major subtypes of breast cancer classified using five immunohistochemical markers: the estrogen receptor and the progesterone receptor (two hormone receptors expressed by luminal cells), the human epidermal growth factors receptor-2 (HER2, a protein marker used to select specific adjuvant therapies), and CK5/6 and EGFR (proteins expressed by basal cells). What Did the Researchers Do and Find? The researchers pooled data on survival time and on the expression of the five immunohistochemical markers from more than 10,000 cases of breast cancer from 12 studies. They then divided the tumors into six subtypes on the basis of their marker expression: luminal (hormone receptor-positive), HER2-positive tumors; luminal, HER2-negative, basal marker-positive tumors; luminal, HER2-negative, basal marker-negative tumors; nonluminal (hormone receptor-negative), HER2-positive tumors; nonluminal, HER2-negative, basal marker-positive tumors; and nonluminal, HER2-negative, basal marker-negative tumors. In the first five years after diagnosis, women with nonluminal tumor subtypes had the worst prognosis but at 15 years after diagnosis, women with luminal HER2-positive tumors had the worst prognosis. Furthermore, death rates (the percentage of affected women dying each year) differed by subtype over time. Thus, women with the two luminal HER2-negative subtypes were as likely to die soon after diagnosis as at later times whereas the death rates associated with nonluminal subtypes peaked within five years of diagnosis and then declined. What Do These Findings Mean? These and other findings indicate that the six subtypes of breast cancer defined by the expression of five immunohistochemical markers have distinct biological characteristics that are associated with important differences in short-term and long-term outcomes. Because different laboratories measured the immunohistochemical markers using different methods, it is possible that some of the tumors included in this study were misclassified. However, the finding of clear differences in the behavior of the immunochemically classified subtypes suggests that the use of the five markers for tumor classification might be robust enough for routine clinical practice. The application of these markers in the clinical setting, suggest the researchers, could improve the targeting of adjuvant therapies to those women most likely to benefit. Furthermore, note the researchers, these findings strongly suggest that subtype-specific responses should be evaluated in future clinical trials of treatments for breast cancer. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000279. This study is further discussed in a PLoS Medicine Perspective by Stefan Ambs The US National Cancer Institute provides detailed information for patients and health professionals on all aspects of breast cancer (in English and Spanish) The American Cancer Society has a detailed guide to breast cancer, which includes information on the immunochemical classification of breast cancer subtypes The UK charities MacMillan Cancer Support and Cancer Research UK also provide detailed information about breast cancer The MedlinePlus Encyclopedia provides information for patients about breast cancer; Medline Plus provides links to many other breast cancer resources (in English and Spanish)
Published: 2010
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33. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor-Negative Breast Cancer Survival

Author: Melissa C. Southey, Paul D.P. Pharoah, Graham G. Giles, Douglas F. Easton, Per Hall, Jonathan Tyrer, Heli Nevanlinna, Henrik Flyger, Kristiina Aittomäki, Caroline Seynaeve, Zachary S. Fredericksen, Jolanta Lissowska, Argyrios Ziogas, Primitiva Menéndez, Børge G. Nordestgaard, Gianluca Severi, Rüdiger Schulz-Wendtland, Angela Cox, Mark E. Sherman, Carl Blomqvist, Vesa Kataja, David Greenberg, Stig E. Bojesen, Tuomas Heikkinen, Javier Benítez, Graeme Elliott, Sara Margolin, Matthias W. Beckmann, Shan Wang-Gohrke, Fergus J. Couch, Roger L. Milne, Rob A. E. M. Tollenaar, Montserrat Garcia-Closas, Arif B. Ekici, Georgia Chenevix-Trench, Arto Mannermaa, Hoda Anton-Culver, Neil E. Caporaso, Veli-Matti Kosma, Kamila Czene, Laura Baglietto, Malcolm W.R. Reed, Xianshu Wang, Kelly L. Bolton, Peter Devilee, Rebecca Hein, José Ignacio Arias, Elizabeth M. Azzato, Janet E. Olson, P. A. Fasching, Manjeet K. Humphreys, Jenny Chang-Claude, Ian W. Brock, Jonathan Beesley, Xiaoqing Chen, and Medical Oncology
Subjects: Oncology, Cancer Research, Genome-wide association study, Bioinformatics, Risk Factors, Receptors, Genotype, education.field_of_study, Tumor, Medicine (all), Single Nucleotide, Articles, Middle Aged, Receptors, Estrogen, Research Design, Female, Human, Adult, medicine.medical_specialty, Population, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Chromosomes, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Biomarkers, Tumor, medicine, Humans, Polymorphism, Allele, education, Alleles, Germ-Line Mutation, Survival analysis, Aged, Proportional Hazards Models, Chromosomes, Human, Pair 15, Pair 15, Membrane Transport Proteins, Cancer, Survival Analysis, medicine.disease, Estrogen, Biomarkers
Abstract: Traditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival. We evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided. In the hypothesis-generating dataset, SNP rs4778137 (C > G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)). The rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.
Published: 2010

34. No evidence that GATA3 rs570613 SNP modifies breast cancer risk

Author: Vernon S. Pankratz, Per Hall, Robert F. Tarrell, Daphne Gschwantler-Kaulich, Manjeet K. Humphreys, Fiona Douglas, Olga M. Sinilnikova, Melissa C. Southey, Noralane M. Lindor, Kirsimari Aaltonen, Graham G. Giles, Carol Chu, Marinus J. Blok, Rob B. van der Luijt, Radka Platte, Andrew K. Godwin, Rosalind A. Eeles, Jonathan Beesley, Anneliese Fink-Retter, Claudine Issacs, Jianjun Liu, Heli Nevanlinna, Antonis C. Antoniou, Christina Justenhoven, Zachary S. Fredericksen, Xiaoqing Chen, Sue Healey, Fiona Lalloo, Tuomas Heikkinen, Carl Blomqvist, Sharon E. Johnatty, D. Gareth Evans, Gabriella Pichert, Trevor Cole, Joan Paterson, Frans B. L. Hogervorst, Marjolijn J. L. Ligtenberg, Hans J. J. P. Gille, Maaike P.G. Vreeswijk, Katherine L. Nathanson, Hiltrud Brauch, Georgia Chenevix-Trench, Margaret Cook, Kristiina Aittomäki, Rosemarie Davidson, Lesley McGuffog, Yon Ko, Amanda B. Spurdle, Maria A. Caligo, Christian F. Singer, Susan M. Domchek, Theo A. M. van Os, Fergus J. Couch, Ute Hamann, Matti A. Rookus, Susan Peock, Christine Fuerhauser, Jackie Cook, Kamila Czene, Caroline Seynaeve, John L. Hopper, Diana Eccles, Shirley Hodgson, Juul T. Wijnen, Douglas F. Easton, Medical Oncology, Neurology, Human genetics, CCA - Oncogenesis, and Human Genetics
Subjects: Cancer Research, Genotype, Genes, BRCA2, Genes, BRCA1, Estrogen receptor, Breast Neoplasms, Single-nucleotide polymorphism, GATA3 Transcription Factor, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Allele, Hereditary cancer and cancer-related syndromes [ONCOL 1], Cancer, medicine.disease, Oncology, Mutation, Cancer research, Female, Breast disease, Mammary gland morphogenesis
Abstract: Contains fulltext : 81267.pdf (Publisher’s version ) (Closed access) GATA-binding protein 3 (GATA3) is a transcription factor that is crucial to mammary gland morphogenesis and differentiation of progenitor cells, and has been suggested to have a tumor suppressor function. The rs570613 single nucleotide polymorphism (SNP) in intron 4 of GATA3 was previously found to be associated with a reduction in breast cancer risk in the Cancer Genetic Markers of Susceptibility project and in pooled analysis of two case-control studies from Norway and Poland (P (trend) = 0.004), with some evidence for a stronger association with estrogen receptor (ER) negative tumours [Garcia-Closas M et al. (2007) Cancer Epidemiol Biomarkers Prev 16:2269-2275]. We genotyped GATA3 rs570613 in 6,388 cases and 4,995 controls from the Breast Cancer Association Consortium (BCAC) and 5,617 BRCA1 and BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). We found no association between this SNP and breast cancer risk in BCAC cases overall (OR(per-allele) = 1.00, 95% CI 0.94-1.05), in ER negative BCAC cases (OR(per-allele) = 1.02, 95% CI 0.91-1.13), in BRCA1 mutation carriers RR(per-allele) = 0.99, 95% CI 0.90-1.09) or BRCA2 mutation carriers (RR(per-allele) = 0.93, 95% CI 0.80-1.07). We conclude that there is no evidence that either GATA3 rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
Published: 2009
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35. Five polymorphisms and breast cancer risk: Results from the breast cancer association consortium

Author: Javier Benitez, José Ignacio Arias, Caroline Baynes, Keun-Young Yoo, Jyh Cherng Yu, Grethe I. Grenaker Alnæs, Alice J. Sigurdson, Irina Coinac, Don M. Conroy, Sara Margolin, Peter Devilee, Matthias W. Beckmann, Ramona Salazar, Heli Nevanlinna, Peter Schürmann, Beata Peplonska, Jolanta Lissowska, Thilo Dörk, Annika Lindblom, Peter A. Fasching, Hoda Anton-Culver, Diana Torres, Vessela N. Kristensen, Jonathan J. Morrison, Henrik Flyger, Christina Justenhoven, Sei Hyun Ahn, Manjeet K. Humphreys, Susan E. Hankinson, Argyrios Ziogoas, Ellen L. Goode, Melissa C. Southey, Fergus J. Couch, Brian E. Henderson, Doug Easton, Kati Kämpjärvi, Veli-Matti Kosma, Marjanka K. Schmidt, Ute Hamann, Amanda B. Spurdle, David G. Cox, Sandrine Tchatchou, Linda Titus-Ernstoff, Peter Kraft, Sascha Abbas, Isabel dos Santos Silva, Laura J. van't Veer, Angela Cox, Stig E. Bojesen, Tuomas Heikkinen, Kirsimari Aaltonen, Kristina Allen-Brady, Laura Baglietto, Paul D.P. Pharoah, Janet E. Olson, Daehee Kang, Christopher A. Haiman, Stephen J. Chanock, Olivia Fletcher, Laurence N. Kolonel, Maaike P.G. Vreeswijk, Jianjun Liu, Loic Le Marchand, Per Hall, Arto Mannermaa, Roger L. Milne, Saeed Rafii, Hiltrud Brauch, Gianluca Severi, Jonathan Beesley, Chen-Yang Shen, Malcolm W.R. Reed, Kamila Czene, Dieter Flesch-Janys, Rob A. E. M. Tollenaar, Claus R. Bartram, Caroline Seynaeve, Graham G. Giles, Rita K. Schmutzler, Reiner Strick, John L. Hopper, Dallas R. English, Flora E. van Leeuwen, Julian Peto, Børge G. Nordestgaard, Yuqing Li, Polly A. Newcomb, Barbara Burwinkel, Jenny Chang-Claude, Pei Ei Wu, Parveen Bhatti, Amy Trentham Dietz, Louise A. Brinton, Natalia Bogdanova, Annegien Broeks, Nicola J. Camp, Gloria Ribas, Arif B. Ekici, Nichola Johnson, Jathine Wong, Montserrat Garcia-Closas, Dong Young Noh, Vesa Kataja, Lisa A. Cannon-Albright, Karen A. Pooley, Georgia Chenevix-Trench, Hui-Chun Wang, David J. Hunter, Carmel Apicella, Alison M. Dunning, Sabapathy P. Balasubramanian, Bruce H. Alexander, Xianshu Wang, Kathleen Egan, and Mia M. Gaudet
Subjects: Oncology, Risk, medicine.medical_specialty, Genotype, Epidemiology, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Polymorphism, Caspase 10, Alleles, 030304 developmental biology, 0303 health sciences, Tumor Necrosis Factor-alpha, BH3 Interacting Domain Death Agonist Protein, Case-Control Studies, DNA-Binding Proteins, Europe, Female, Intracellular Signaling Peptides and Proteins, Logistic Models, Nuclear Proteins, Case-control study, Cancer, Odds ratio, Single Nucleotide, medicine.disease, 3. Good health, Minor allele frequency, Endocrinology, 030220 oncology & carcinogenesis, Breast disease
Abstract: Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between-study heterogeneity for associations with risk for single-nucleotide polymorphisms (SNP) in CASP10, PGR, and BID. Estimates were imprecise for women of Asian and African descent due to small numbers and lower minor allele frequencies (with the exception of BID SNP). The ORs for each copy of the minor allele were not significantly different by estrogen or progesterone receptor status, nor were any significant interactions found between the polymorphisms and age or family history of breast cancer. In conclusion, our data provide persuasive evidence against an overall association between invasive breast cancer risk and ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 genotypes among women of European descent. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1610–6)
Published: 2009

36. Genome-wide association analysis identifies three new breast cancer susceptibility loci

Author: William J. Tapper, Frederik Marmé, Natalia Bogdanova, Joe Dennis, Pei-Ei Wu, Vesa Kataja, Michael Jones, Dong-Young Noh, Xiaoqing Chen, Thilo Dörk, Javier Benitez, Arif B. Ekici, André G. Uitterlinden, Karin Leunen, Chen-Yang Shen, Esther M. John, Sune F. Nielsen, Adam M. Lee, Arto Mannermaa, Dieter Flesch-Janys, Diana Eccles, Don M. Conroy, Quinten Waisfisz, Sara Margolin, Hoda Anton-Culver, Peter Devilee, Ans M.W. van den Ouweland, Ruth Swann, Chia-Ni Hsiung, Peter Schürmann, Per Hall, Bertram Müller-Myhsok, Jonathan Beesley, Graham G. Giles, Qin Wang, Mitul Shah, Matthias W. Beckmann, Veli-Matti Kosma, Carmel Apicella, Henrik Flyger, Daniel F. Schmidt, Gianluca Severi, Kristen N. Stevens, Paolo Peterlongo, Helen Tsimiklis, Betül T. Yesilyurt, Irene L. Andrulis, Louiza S. Velentzis, Peter A. Fasching, Jyh-Cherng Yu, Caroline Baynes, Jenny Chang-Claude, Craig Luccarini, Leslie Bernstein, Katarzyna Durda, Antoinette Hollestelle, Catriona McLean, Georgia Chenevix-Trench, Rebecca Hein, Heli Nevanlinna, Arja Jukkola-Vuorinen, Jolanta Lissowska, Rita K. Schmutzler, Giuseppe Floris, Christa Stegmaier, David J. Hunter, Kristiina Aittomäki, Johann H. Karstens, Alan Ashworth, Alfons Meindl, Emilie Cordina-Duverger, Stefan Nickels, Julian Peto, Jan Lubinski, Børge G. Nordestgaard, Ed Dicks, Stig E. Bojesen, Christie J. van Asperen, Malcolm W.R. Reed, Michael J. Kerin, Annika Lindblom, Barbara Burwinkel, Kristy Driver, Darya Prokofieva, Montserrat Garcia-Closas, Thomas Brüning, Christina Justenhoven, Nazneen Rahman, Annegien Broeks, Hermann Brenner, Hiltrud Brauch, Laura Baglietto, Yuri I. Rogov, Clare Turnbull, A Jakubowska, Marina Bermisheva, Heiko Müller, Hanne Meijers-Heijboer, Anne-Lise Børrensen-Dale, Pascal Guénel, Stephen J. Chanock, Siranoush Manoukian, Melissa C. Southey, Daniel J. Park, M. Rosario Alonso, Christof Sohn, Shan Wang-Gohrke, Melanie Maranian, Shahana Ahmed, Jonine D. Figueroa, Robert Winqvist, Jianjun Liu, Suthee Rattanamongkongul, Diether Lambrechts, Andreas Schneeweiss, Paul D.P. Pharoah, Alexander Miron, Ursula Eilber, Angela Cox, Anna González-Neira, Minh Bui, Frans B. L. Hogervorst, Peter Hillemanns, Peter Lichtner, Maartje J. Hooning, Roger L. Milne, Alison M. Dunning, Fernando Rivadeneira, Ian Tomlinson, Thérèse Truong, Volker Arndt, Rogier A. Oldenburg, Grethe I. Grenaker Alnæs, Senno Verhoef, Rob A. E. M. Tollenaar, Anna Marie Mulligan, Kenneth Muir, Christina Clarke Dur, Katarzyna Jaworska, Saila Kauppila, Olivia Fletcher, Jaana M. Hartikainen, Michael P. Lux, Kyriaki Michailidou, Stefano Fortuzzi, Douglas F. Easton, Anthony J. Swerdlow, Elza Khusnutdinova, Annie Perkins, Carl Blomqvist, Argyrios Ziogas, Keun-Young Yoo, Caroline Seynaeve, Natalia Antonenkova, Bruce A.J. Ponder, Vessela N. Kristensen, Gord Glendon, Daehee Kang, Elinor J. Sawyer, Michael Bremer, Louise A. Brinton, Minouk J. Schoemaker, Kamila Czene, Isabel dos Santos Silva, John L. Hopper, Astrid K. Irwanto, Nick Orr, S Gerty, Fergus J. Couch, Arkom Chaiwerawattana, Manjeet K. Humphreys, Marjanka K. Schmidt, Maya Ghoussaini, Nikki Graham, Artitaya Lophatananon, Florence Menegaux, Enes Makalic, Katri Pylkäs, Nichola Johnson, Xianshu Wang, Bernardo Bonanni, Mark Lathrop, Human genetics, CCA - Oncogenesis, Clinical Genetics, Internal Medicine, Medical Oncology, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, and Human Genetics
Subjects: Candidate gene, Chromosomes,Human,Pair 21, analysis, cell carcinoma, Mammary gland, Estrogen receptor, Genome-wide association study, developmental regulatory molecule, 0302 clinical medicine, common variants, retinoic acid, Pair 12, genetics, hormone-related protein, Genetics, Chromosomes,Human,Pair 12, Treatment - Localised Therapies – Discovery and Development, Principal Component Analysis, 0303 health sciences, Bone metastasis, Single Nucleotide, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, epidemiology, Cancer Type - Breast Cancer, Female, Human, Risk, ulnar-mammary syndrome, parathyroid-hormone, European Continental Ancestry Group, Breast Neoplasms, Biology, Chromosomes, Polymorphism,Single Nucleotide, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], Genetic predisposition, medicine, cancer, Humans, Women, Genetic Predisposition to Disease, Polymorphism, Genetics and epigenetic pathways of disease Translational research [NCMLS 6], breast, 030304 developmental biology, Hereditary cancer and cancer-related syndromes [ONCOL 1], Cancer, confer susceptibility, medicine.disease, gene-expression, Logistic Models, negative-feedback, Genetic Loci, Cancer research, Other, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 21, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pair 21, Meta-Analysis
Abstract: Item does not contain fulltext Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for approximately 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in approximately 70,000 cases and approximately 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.
Published: 2012
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37. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Author: Malcolm W.R. Reed, Artitaya Lophatananon, M. Pilar Zamora, Chen-Yang Shen, Monica Barile, Suleeporn Sangrajrang, Nichola Johnson, James McKay, Ming-Feng Hou, Diether Lambrechts, Isabel dos Santos Silva, Paolo Radice, Thilo Dörk, Janet E. Olson, Grethe I. Grenaker Alnæs, Katarzyna Durda, Angela Cox, Javier Benitez, Maartje J. Hooning, Douglas F. Easton, Volker Arndt, Hui Zhao, Nick Orr, Heli Nevanlinna, Leslie Bernstein, Jose Ignacio Arias Perez, Hoda Anton-Culver, Nicola Miller, Jolanta Lissowska, Natalia Bogdanova, Frans B. L. Hogervorst, Manjeet K. Humphreys, Johann H. Karstens, Alfons Meindl, Veli-Matti Kosma, Mark E. Sherman, Montserrat Garcia-Closas, Pascal Guénel, Zachary S. Fredericksen, Alison M. Dunning, Kenneth Offit, Marjanka K. Schmidt, Katarzyna Jaworska, Yon Ko, Heiko Müller, Jyh Cherng Yu, Melissa C. Southey, Paul Brennan, Kenneth Muir, Maya Ghoussaini, Laura Baglietto, Antonis C. Antoniou, Sheila Seal, Robert Winqvist, Siranoush Manoukian, Peter Schürmann, Anne Lise Børresen-Dale, Rita K. Schmutzler, Julian Peto, Linda J. Titus, Ian W. Brock, Valerie Gaborieau, Miroslaw K. Kapuscinski, Iosif V. Zalutsky, Arja Jukkola-Vuorinen, Peter A. Fasching, Elza Khusnutdinova, Jaana M. Hartikainen, Børge G. Nordestgaard, Jianjun Liu, Barbara Burwinkel, Anthony J. Swerdlow, Suthee Rattanamongkongul, Florence Menegaux, Hermann Brenner, Mervi Grip, Michael J. Kerin, Rebecca Hein, Simon S. Cross, Mia M. Gaudet, Anna Jakubowska, Paul D.P. Pharoah, Alexander Miron, Keun-Young Yoo, Katri Pylkäs, Huan Ming Hsu, Per Hall, Christa Stegmaier, Patrick Neven, H. Bas Bueno-de-Mesquit, Dieter Flesch-Janys, Sara Margolin, Jonine D. Figueroa, Natalia Antonenkova, Peter Hillemanns, Elżbieta Złowocka, Matthias W. Beckmann, Julia A. Knight, Alan Ashworth, Catriona McLean, Georgia Chenevix-Trench, Mark E. Robson, Arto Mannermaa, Roger L. Milne, Dong Young Noh, Nazneen Rahman, Hiltrud Brauch, Carl Blomqvist, Darya Prokovieva, Vesa Kataja, Kristiina Aittomäki, Annegien Broeks, Keith Humpreys, Marina Bermisheva, Sarah Schott, Ian Tomlinson, Thérèse Truong, Anna Marie Mulligan, Irene L. Andrulis, Christof Sohn, Olivia Fletcher, Gord Glendon, Annika Lindblom, Graham G. Giles, Kamila Czene, Xiaoqing Chen, Esther M. John, Claus R. Bartram, John L. Hopper, Fergus J. Couch, Kathleen M. Egan, Ute Hamann, Stig E. Bojesen, Vessela N. Kristensen, Tuomas Heikkinen, Clare Turnbull, Alexander Hein, Emilie Cordina-Duverger, Stefan Nickels, Daehee Kang, Arif B. Ekici, Frederick Marmee, Elinor J. Sawyer, Minouk J. Schoemaker, Jenny Chang-Claude, Argyrios Ziogas, Caroline Seynaeve, Joseph Vijai, Anthony Renwick, Jonathan Beesley, Paolo Peterlongo, Jonathan J. Morrison, Henrik Flyger, Andreas Schneeweiss, John W.M. Martens, Xianshu Wang, Puttisak Puttawibul, Christina A. Clarke, Daniel J. Park, Shan Wang-Gohrke, Melanie Maranian, Shahana Ahmed, Polly A. Newcomb, Hans Wildiers, Amy Trentham-Dietz, Albina Farahtdinova, Gianluca Severi, Margriet Collée, Clinical Genetics, Medical Oncology, Department of Obstetrics and Gynecology, Women's Health Research Program, Department of Medical and Clinical Genetics, Clinicum, Department of Oncology, and Genome-Scale Biology (GSB) Research Program
Subjects: Life Sciences & Biomedicine - Other Topics, Genetics and Molecular Biology (all), Oncology, Linkage disequilibrium, Epidemiology, susceptibility locus, Estrogen receptor, Genome-wide association study, chinese, Bioinformatics, Biochemistry, Linkage Disequilibrium, 0302 clinical medicine, Risk Factors, Receptors, SUSCEPTIBILITY LOCUS, 0303 health sciences, Multidisciplinary, Medicine (all), Cancer Risk Factors, Statistics, Obstetrics and Gynecology, WOMEN, Single Nucleotide, Genomics, 3. Good health, Europe, Multidisciplinary Sciences, Receptors, Estrogen, 030220 oncology & carcinogenesis, Genetic Epidemiology, Medicine, Science & Technology - Other Topics, Chromosomes, Human, Pair 6, Female, Pair 6, women, Cancer Epidemiology, Human, Research Article, medicine.medical_specialty, Asia, Breast Neoplasms, Haplotypes, Humans, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Genome-Wide Association Study, Biochemistry, Genetics and Molecular Biology (all), Agricultural and Biological Sciences (all), Science, education, Genetic Causes of Cancer, Single-nucleotide polymorphism, Biostatistics, Chromosomes, RC0254, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Genome Analysis Tools, Internal medicine, Breast Cancer, medicine, Genome-Wide Association Studies, Genetics, Cancer Genetics, SNP, Polymorphism, Biology, Genetic Association Studies, 030304 developmental biology, Science & Technology, business.industry, Haplotype, Computational Biology, Human Genetics, Odds ratio, medicine.disease, Estrogen, Genetics of Disease, 3111 Biomedicine, business, CHINESE, Mathematics
Abstract: The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10(-7), p(heterogeneity) = 5.1×10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours. ispartof: PLoS One vol:7 issue:8 ispartof: location:United States status: published
Published: 2012
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38. Abstract 870: Analysis of breast cancer risk factors by expression of tumor markers: results of 34 studies in the Breast Cancer Association Consortium (BCAC)

Author: Heli Nevanlinna, Ellen L. Goode, Manjeet K. Humphreys, Amanda B. Spurdle, Marjanka K. Schmidt, Mia M. Gaudet, Paul D.P. Pharoah, Roger L. Milne, Fergus J. Couch, Douglas F. Easton, Jenny Chang-Claude, Xiaohong (Rose) Yang, Mark E. Sherman, Peter A. Fasching, and Montserrat Garcia-Closas
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Breast cancer, business.industry, Internal medicine, Medicine, business, medicine.disease
Abstract: Epidemiologic studies suggest that breast cancer risk factor associations vary by tumor marker expression; however, individual studies have had limited power to address this question. We pooled data from up to 35,568 invasive breast cancer cases from 34 studies participating in the Breast Cancer Association Consortium (BCAC) to evaluate associations between established risk factors (age at menarche, nulliparity, age at first full time birth [AFFTB], body mass index [BMI] and family history) and breast cancer subtypes, defined by immunohistochemical expression of ER, PR, HER2, and basal markers (CK5/6 or CK5, EGFR). We used polychotomous logistic regression to evaluate relationships between risk factors and tumor subtypes in case-only analyses and to estimate case-control odds ratios and 95% confidence intervals for the associations between risk factors and specific tumor subtypes in 11 population-based studies including up to 12,841 cases and 17,032 controls. In case-only analyses, we found that reproductive risk factors were more common in hormone receptor positive tumors: early age at menarche was most strongly related to PR status (34.6% vs. 32.4% of women with age at menarche ≤12 years among PR+ and PR- cases, respectively, P= 0.001); whereas nulliparity, and late AFFTB in parous women were most strongly related to ER status (15.3% vs. 13.6% nulliparous women, 17.1% vs. 15.2% women with late AFFTB [≥30 years], among ER+ and ER- cases, respectively, P=2.6×10−6 for nulliparity and P=2.0×10−7 for late AFFTB). Nulliparity and late AFFTB were less common among triple negative (TN) tumors overall and among TN tumors expressing basal markers. Elevated BMI in women aged 50 years or younger was more common in ER-&PR- than ER+&PR+ tumors (17.0% vs 13.6% women with BMI ≥30, respectively, P=1.3×10−7), whereas above age 50 years, elevated BMI was more common in ER+&PR+ than ER+&PR- tumors (20.9% vs 16.7% women with BMI ≥30, respectively, P=2.8×10−8 comparing BMI ≥30 to BMI Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 870.
Published: 2010
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39. Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients

Author: Thilo Dörk, Douglas F. Easton, Paul D.P. Pharoah, Scarlett Reincke, Laura J. van't Veer, Flora E. van Leeuwen, Mitul Shah, Johanna Tommiska, Rainer Fagerholm, Manjeet K. Humphreys, Marjanka K. Schmidt, Annegien Broeks, Carl Blomqvist, Heli Nevanlinna, Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
Subjects: Oncology, Adult, medicine.medical_specialty, Genotype, Single-nucleotide polymorphism, Breast Neoplasms, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Breast cancer, Germline mutation, Surgical oncology, Internal medicine, Research article, medicine, Humans, skin and connective tissue diseases, Survival rate, Germ-Line Mutation, 030304 developmental biology, Aged, Aged, 80 and over, Medicine(all), 0303 health sciences, biology, Proto-Oncogene Proteins c-mdm2, Middle Aged, medicine.disease, Prognosis, Genes, p53, Immunohistochemistry, 3. Good health, Survival Rate, Editorial, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Mdm2, Female, Tumor Suppressor Protein p53
Abstract: INTRODUCTION: Somatic inactivation of the TP53 gene in breast tumors is a marker for poor outcome, and breast cancer outcome might also be affected by germ-line variation in the TP53 gene or its regulators. We investigated the effects of the germ-line single nucleotide polymorphisms TP53 R72P (215G>C) and MDM2 SNP309 (-410T>G), and p53 protein expression in breast tumors on survival. METHODS: We pooled data from four breast cancer cohorts within the Breast Cancer Association Consortium for which both TP53 R72P and MDM2 SNP309 were genotyped and follow-up was available (n = 3,749). Overall and breast cancer-specific survival analyses were performed using Kaplan-Meier analysis and multivariate Cox's proportional hazards regression models. RESULTS: Survival of patients did not differ by carriership of either germ-line variant, R72P (215G>C) or SNP309 (-410G>T) alone. Immunohistochemical p53 staining of the tumor was available for two cohorts (n = 1,109 patients). Survival was worse in patients with p53-positive tumors (n = 301) compared to patients with p53-negative tumors (n = 808); breast cancer-specific survival: HR 1.6 (95% CI 1.2 to 2.1), P = 0.001. Within the patient group with p53-negative tumors, TP53 rare homozygous (CC) carriers had a worse survival than G-allele (GG/GC) carriers; actuarial breast cancer-specific survival 71% versus 80%, P = 0.07; HR 1.8 (1.1 to 3.1), P = 0.03. We also found a differential effect of combinations of the two germ-line variants on overall survival; homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers; actuarial overall survival (GG versus TT/TG) 64% versus 75%, P = 0.001; HR (GG versus TT) 1.5 (1.1 to 2.0), P = 0.01. We found no evidence for a differential effect of MDM2 SNP309 by p53 protein expression on survival. CONCLUSIONS: The TP53 R72P variant may be an independent predictor for survival of patients with p53-negative tumors. The combined effect of TP53 R72P and MDM2 SNP309 on survival is in line with our a priori biologically-supported hypothesis, that is, the role of enhanced DNA repair function of the TP53 Pro-variant, combined with increased expression of the Mdm2 protein, and thus overall attenuation of the p53 pathway in the tumor cells.
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40. The role of genetic breast cancer susceptibility variants as prognostic factors

Author: Laura J. van't Veer, John W.M. Martens, Erik Van Limbergen, Jenny Chang-Claude, Alison M. Dunning, Sabapathy P. Balasubramanian, Janet E. Olson, Sara Margolin, Mitul Shah, Matthias W. Beckmann, Malcolm W.R. Reed, Manjeet K. Humphreys, Mark E. Sherman, Douglas F. Easton, Graham G. Giles, Anne Sophie Dieudonne, Bernardo Bonanni, Marjanka K. Schmidt, Saila Kauppila, Thilo Dörk, Michael Bremer, Arja Jukkola-Vuorinen, Peter A. Fasching, Sara J. Schonfeld, Laura Baglietto, Annegien Broeks, Stig E. Bojesen, Stefan Nickels, Carl Blomqvist, Kamila Czene, Javier Benitez, Hilmi Ozcelik, John L. Hopper, Frederik Marmé, Paolo Peterlongo, Simon S. Cross, Melissa C. Southey, Maria Schiekel, Robert Winqvist, Paul D.P. Pharoah, Alexander Miron, Agnes Jager, Jose Ignacio Arias Perez, M. Pilar Zamora, Esther M. John, Matthew L. Kosel, Diether Lambrechts, Henrik Flyger, Sigrid Hatse, Tjoung Won Park-Simon, Per Hall, Petra E A Huijts, Jonine D. Figueroa, Irene L. Andrulis, Dario Greco, Hoda Anton-Culver, Veli-Matti Kosma, Kelly-Anne Phillips, Arto Mannermaa, Claudia Rauh, Fergus J. Couch, Andreas Schneeweiss, Flora E. van Leeuwen, Kristen N. Stevens, Annika Lindblom, Bernard Peissel, Georgia Chenevix-Trench, Arif B. Ekici, Preetha Rajaraman, Shan Wang-Gohrke, Dennis J. Slamon, Jianjun Liu, M.J. Hooning, Jaana M. Hartikainen, Montserrat Garcia-Closas, Katri Pylkäs, Roger L. Milne, Christof Sohn, Peter Devilee, Gianluca Severi, Ursula Eilber, Kristiina Aittomäki, Vesa Kataja, Børge G. Nordestgaard, Rob A. E. M. Tollenaar, Anna Marie Mulligan, Argyrios Ziogas, Barbara Burwinkel, Caroline Seynaeve, Bernard Loris, Mieke Kriege, Renate Udo, Gord Glendon, Carmel Apicella, Heli Nevanlinna, Thomas Karn, Jolanta Lissowska, Angela Cox, and Medical Oncology
Subjects: Genome-wide association study, 0302 clinical medicine, Risk Factors, Databases, Genetic, Receptors, Association Studies Article, Genetics (clinical), 0303 health sciences, education.field_of_study, Hazard ratio, Homozygote, General Medicine, Single Nucleotide, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Population, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Databases, Breast cancer, Genetic, SDG 3 - Good Health and Well-being, medicine, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, education, Molecular Biology, 030304 developmental biology, Genetic association, Proportional Hazards Models, Neoplastic, Proportional hazards model, medicine.disease, Estrogen, Genetics, Population, TOX3, Gene Expression Regulation, Genetic Loci, Cancer research
Abstract: Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P

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