Cited by 178BRCA gene mutations in cancerBreast Lesions and CarcinomasGenetic Associations and Epidemiology

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Age- and Tumor Subtype–Specific Breast Cancer Risk Estimates for CH EK 2 *1100delC Carriers

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Schmidt, Marjanka K., Hogervorst, Frans, van Hien, Richard, Cornelissen, Sten, Broeks, Annegien, Adank, Muriel A., Meijers, Hanne, Waisfisz, Quinten, Hollestelle, Antoinette, Schutte, Mieke, van den Ouweland, Ans, Hooning, Maartje, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Antoniou, Antonis C., Arndt, Volker, Bermisheva, Marina, Bogdanova, Natalia V., Bolla, Manjeet K., Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Dunning, Alison M., Fasching, Peter A., Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Galle, Eva, García-Closas, Montserrat, Giles, Graham G., Haeberle, Lothar, Hall, Per, Hillemanns, Peter, Hopper, John L., Jakubowska, Anna, John, Esther M., Jones, Michael, Khusnutdinova, Elza, Knight, Julia A., Kosma, Veli-Matti, Kristensen, Vessela, Lee, Andrew, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Meindl, Alfons, Milne, Roger L., Muranen, Taru A., Newcomb, Polly A., Offit, Kenneth, Park-Simon, Tjoung-Won, Peto, Julian, Pharoah, Paul D.P., Robson, Mark, Rudolph, Anja, Sawyer, Elinor J., Schmutzler, Rita K., Seynaeve, Caroline, Soens, Julie, Southey, Melissa C., Spurdle, Amanda B., Surowy, Harald, Swerdlow, Anthony, Tollenaar, Rob A.E.M., Tomlinson, Ian, Trentham-Dietz, Amy, Vachon, Celine, Wang, Qin, Whittemore, Alice S., Ziogas, Argyrios, van der Kolk, Lizet, Nevanlinna, Heli, Dörk, Thilo, Bojesen, Stig, Easton, Douglas F.·2016·Journal of Clinical Oncology

DOI 10.1200/jco.2016.66.5844PMC PMC5019754

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Abstract

Purpose: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. Patients and Methods: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Results: Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center–based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10 −20 ). The OR was higher for estrogen receptor (ER)–positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10 −21 ]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10 −4 ). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. Conclusion: These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up.

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Authors: Schmidt, M. K., Hogervorst, F., van Hien, R., Cornelissen, S., Broeks, A., Adank, M. A., Meijers, H., Waisfisz, Q., Hollestelle, A., Schutte, M., van den Ouweland, A., Hooning, M., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Antoniou, A. C., Arndt, V., Bermisheva, M., Bogdanova, N. V., Bolla, M. K., Brauch, H., Brenner, H., Brüning, T., Burwinkel, B., Chang-Claude, J., Chenevix-Trench, G., Couch, F. J., Cox, A., Cross, S. S., Czene, K., Dunning, A. M., Fasching, P. A., Figueroa, J., Fletcher, O., Flyger, H., Galle, E., García-Closas, M., Giles, G. G., Haeberle, L., Hall, P., Hillemanns, P., Hopper, J. L., Jakubowska, A., John, E. M., Jones, M., Khusnutdinova, E., Knight, J. A., Kosma, V.-M., Kristensen, V., Lee, A., Lindblom, A., Lubinski, J., Mannermaa, A., Margolin, S., Meindl, A., Milne, R. L., Muranen, T. A., Newcomb, P. A., Offit, K., Park-Simon, T.-W., Peto, J., Pharoah, P. D. P., Robson, M., Rudolph, A., Sawyer, E. J., Schmutzler, R. K., Seynaeve, C., Soens, J., Southey, M. C., Spurdle, A. B., Surowy, H., Swerdlow, A., Tollenaar, R. A. E. M., Tomlinson, I., Trentham-Dietz, A., Vachon, C., Wang, Q., Whittemore, A. S., Ziogas, A., van der Kolk, L., Nevanlinna, H., Dörk, T., Bojesen, S., & Easton, D. F.
Affiliations: F. Hoffmann-La Roche AG (CH)
Marjanka K. Schmidt, Frans Hogervorst, Richard van Hien, Sten Cornelissen, Annegien Broeks, and Lizet van der Kolk, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital; Muriel A. Adank, Hanne Meijers, and Quinten Waisfisz, VU University Medical Center, Amsterdam; Antoinette Hollestelle, Mieke Schutte, Maartje Hooning, and Caroline Seynaeve, Erasmus MC Cancer Institute; Ans van den Ouweland, Erasmus University Medical Center, Rotterdam; Rob A.E.M. Tollenaar, Leiden University Medical Center,...
Corresponding author: Schmidt, Marjanka K.
ORCID: Schmidt, Marjanka K.
Cornelissen, Sten
Broeks, Annegien
Adank, Muriel A.
Waisfisz, Quinten
Hollestelle, Antoinette
Hooning, Maartje
Andrulis, Irene L.
Antoniou, Antonis C.
Arndt, Volker
Bermisheva, Marina
Bogdanova, Natalia V.
Bolla, Manjeet K.
Brauch, Hiltrud
Brenner, Hermann
Brüning, Thomas
Burwinkel, Barbara
Chang-Claude, Jenny
Couch, Fergus J.
Cox, Angela
Cross, Simon S.
Czene, Kamila
Dunning, Alison M.
Fasching, Peter A.
Figueroa, Jonine
Fletcher, Olivia
Galle, Eva
Giles, Graham G.
Hall, Per
Hillemanns, Peter
Hopper, John L.
Jakubowska, Anna
John, Esther M.
Knight, Julia A.
Kosma, Veli-Matti
Kristensen, Vessela
Lindblom, Annika
Margolin, Sara
Milne, Roger L.
Muranen, Taru A.
Newcomb, Polly A.
Pharoah, Paul D.P.
Robson, Mark
Rudolph, Anja
Sawyer, Elinor J.
Southey, Melissa C.
Spurdle, Amanda B.
Surowy, Harald
Swerdlow, Anthony
Tollenaar, Rob A.E.M.
Tomlinson, Ian
Vachon, Celine
Wang, Qin
Whittemore, Alice S.
Ziogas, Argyrios
Nevanlinna, Heli
Dörk, Thilo
Bojesen, Stig
Easton, Douglas F.
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2016-08-10
Volume: 34
Issue: 23
Pages: 2750-2760
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2016.66.5844
PMC: PMC5019754
OpenAlex: W2400927555
Cited by: 173
References: 27
Citations by year: 2026: 5 · 2025: 1 · 2024: 16 · 2023: 17 · 2022: 30 · 2021: 19 · 2020: 19 · 2019: 27 · 2018: 22 · 2017: 14 · 2016: 3
FWCI: 17.59
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed Central (publishedVersion)
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Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
Pure Amsterdam UMC (publishedVersion, other-oa)
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Funders: U.S. Department of Health and Human Services
Susan G. Komen for the Cure (CA116201, 39346, DDHK 2009-4318, 70492, 193387/V50, C1287/A10118, 01KW9976/8, DDHK 2004-3124, HEALTH-F2-2009-223175, CA92044, LVS39420, 01KW9975/5, 2007-3839, CA58860, 01KW9977/0, 2009 4363, 193387/H10, BBMRI-NL CP16, RUS08/017, 209057, 110837, 01KW0114, RUL 1997-1505, PBZ_KBN_122/P05/2004, UM1 CA164920, C490/A10124)
Mayo Clinic (CA116201)
Breast Cancer Research Foundation (UM1 CA164920, C490/A10124, 2007-3839, 39346, 01KW0114, 70492, 01KW9977/0, DDHK 2009-4318, C1287/A10118, CA116201, 01KW9976/8, RUL 1997-1505, CA92044, 209057, 110837, RUS08/017, BBMRI-NL CP16, CA58860, 2009 4363, LVS39420, 01KW9975/5, 193387/V50, 193387/H10, PBZ_KBN_122/P05/2004, HEALTH-F2-2009-223175, DDHK 2004-3124)
Memorial Sloan-Kettering Cancer Center
Itä-Suomen Yliopisto (RUL 1997-1505, 110837, DDHK 2009-4318, CA92044, LVS39420, 70492, 2007-3839, 193387/V50, C1287/A10118, PBZ_KBN_122/P05/2004, RUS08/017, C490/A10124, 193387/H10, 01KW9977/0, CA116201, 39346, 209057, 2009 4363, UM1 CA164920, HEALTH-F2-2009-223175, BBMRI-NL CP16, 01KW9976/8, 01KW9975/5, CA58860, DDHK 2004-3124, 01KW0114)
Helsingin Yliopisto
Helsingin ja Uudenmaan Sairaanhoitopiiri
Sundhed og Sygdom, Det Frie Forskningsråd (C1287/A10118, DDHK 2009-4318, 39346, PBZ_KBN_122/P05/2004, CA116201, HEALTH-F2-2009-223175, 01KW9977/0, CA92044, UM1 CA164920, 01KW9975/5, LVS39420, CA58860, RUS08/017, 70492, C490/A10124, 01KW0114, 2007-3839, 193387/H10, 01KW9976/8, 209057, 2009 4363, BBMRI-NL CP16, 193387/V50, DDHK 2004-3124, 110837, RUL 1997-1505)
Deutsches Krebsforschungszentrum (PBZ_KBN_122/P05/2004, 110837, 01KW9976/8, DDHK 2004-3124, UM1 CA164920, 01KW9977/0, 01KW0114, RUS08/017, 193387/H10, C490/A10124, 2009 4363, 70492, 193387/V50, C1287/A10118, CA116201, 2007-3839, CA92044, HEALTH-F2-2009-223175, LVS39420, BBMRI-NL CP16, CA58860, 209057, DDHK 2009-4318, 01KW9975/5, RUL 1997-1505, 39346)
Kreftforeningen (BBMRI-NL CP16, PBZ_KBN_122/P05/2004, UM1 CA164920, RUL 1997-1505, 70492, DDHK 2009-4318, HEALTH-F2-2009-223175, 2009 4363, 2007-3839, C1287/A10118, 193387/V50, DDHK 2004-3124, 39346, CA58860, 01KW9975/5, 209057, RUS08/017, 193387/H10, C490/A10124, 01KW0114, 110837, 01KW9976/8, LVS39420, CA116201, CA92044, 01KW9977/0)
London School of Hygiene and Tropical Medicine
David F. and Margaret T. Grohne Family Foundation (01KW9977/0, CA92044, 01KW9975/5, 2009 4363, PBZ_KBN_122/P05/2004, UM1 CA164920, BBMRI-NL CP16, CA58860, C1287/A10118, 70492, CA116201, DDHK 2009-4318, C490/A10124, 110837, DDHK 2004-3124, 209057, HEALTH-F2-2009-223175, 2007-3839, 193387/V50, RUL 1997-1505, 193387/H10, 01KW0114, 39346, 01KW9976/8, RUS08/017, LVS39420)
Wellcome Trust (090532, 090532/Z/09/Z)
Francis Crick Institute (10124, 10119)
QIMR Berghofer Medical Research Institute
Lon V. Smith Foundation (01KW0114, LVS39420, 70492, RUS08/017, 01KW9975/5, DDHK 2009-4318, C490/A10124, 209057, CA116201, PBZ_KBN_122/P05/2004, UM1 CA164920, 2007-3839, 01KW9976/8, 01KW9977/0, C1287/A10118, BBMRI-NL CP16, 110837, CA92044, HEALTH-F2-2009-223175, CA58860, RUL 1997-1505, DDHK 2004-3124, 2009 4363, 39346, 193387/H10, 193387/V50)
Cancer Research UK (LVS39420, 223175, 11174, 70492, 10119, 01KW9977/0, C1287/A10118, C1287/A12014, RUS08/017, C1287‐A10118, 12014, HEALTHF2-2009-223175, 16561, 01KW9975/5, 16565, RUL 1997-1505, 209057, C1287/ A12014, 110837, C1287, CA92044, PBZ_KBN_122/P05/2004, 20861, 2007-3839, 01KW9976/8, 193387/V50, 10118, CA116201, 10124, 2009 4363, DDHK 2004-3124, C490/A10124, UM1 CA164920, 39346, 01KW0114, CA58860, 193387/H10, BBMRI-NL CP16, DDHK 2009-4318)
National Institute for Health and Care Research (110837, 39346, RUS08/017, 193387/V50, 01KW9976/8, HEALTH-F2-2009-223175, 03/DHCS/03/G121/51, DDHK 2009-4318, PBZ_KBN_122/P05/2004, 209057, CA116201, CA92044, C1287/A10118, 01KW9975/5, BBMRI-NL CP16, 01KW9977/0, RUL 1997-1505, 70492, UM1 CA164920, LVS39420, DDHK 2004-3124, 2009 4363, 01KW0114, CA58860, 2007-3839, C490/A10124, 193387/H10)
King's College London
University of Oxford
National Breast Cancer Foundation (01KW9975/5, LVS39420, 2009 4363, HEALTH-F2-2009-223175, BBMRI-NL CP16, 39346, CA116201, RUS08/017, 193387/H10, 110837, CA58860, DDHK 2009-4318, DDHK 2004-3124, 2007-3839, 01KW9977/0, 193387/V50, 01KW9976/8, C490/A10124, RUL 1997-1505, 70492, CA92044, 01KW0114, 209057, UM1 CA164920, C1287/A10118, PBZ_KBN_122/P05/2004)
Agency for Science, Technology and Research
Robert Bosch Stiftung (01KW9976/8, 193387/H10, 01KW0114, DDHK 2009-4318, DDHK 2004-3124, C1287/A10118, UM1 CA164920, 70492, BBMRI-NL CP16, RUS08/017, CA116201, CA92044, HEALTH-F2-2009-223175, 01KW9977/0, 01KW9975/5, 193387/V50, 2009 4363, C490/A10124, 39346, PBZ_KBN_122/P05/2004, 110837, RUL 1997-1505, CA58860, 2007-3839, 209057, LVS39420)
Universität Heidelberg
Universiteit Leiden
University of Melbourne
Universiteit van Amsterdam
Vrije Universiteit Amsterdam
Eberhard Karls Universität Tübingen
Bundesministerium für Bildung und Forschung (193387/V50, 2007-3839, 70492, BBMRI-NL CP16, 01KW9977/0, 39346, 01KW9975/5, 01KW9976/8, 2009 4363, C1287/A10118, C490/A10124, HEALTH-F2-2009-223175, 01KW0114, PBZ_KBN_122/P05/2004, RUS08/017, 110837, CA92044, CA58860, DDHK 2009-4318, CA116201, UM1 CA164920, 193387/H10, RUL 1997-1505, 209057, LVS39420, DDHK 2004-3124)
Cancerfonden
Gentofte Hospital
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (184021007, NWO 184.021.007)
Deutsche Gesetzliche Unfallversicherung
Herlev Hospital
University of Toronto
Karolinska Institutet (DDHK 2004-3124, 01KW9977/0, 39346, C1287/A10118, CA58860, HEALTH-F2-2009-223175, DDHK 2009-4318, LVS39420, CA116201, PBZ_KBN_122/P05/2004, RUL 1997-1505, RUS08/017, 2009 4363, C490/A10124, CA92044, 01KW9975/5, 01KW0114, 193387/H10, UM1 CA164920, BBMRI-NL CP16, 193387/V50, 110837, 70492, 01KW9976/8, 2007-3839, 209057)
Kuopion Yliopistollinen Sairaala
Stockholms Läns Landsting
KWF Kankerbestrijding (193387/V50, NKI 2007–3839; 2009 4363, PBZ_KBN_122/P05/2004, DDHK 2004‐3124, 2007-3839, 2004-3124, LVS39420, RUS08/017, 01KW9976/8, UM1 CA164920, 70492, 1997-1505, HEALTH-F2-2009-223175, C490/A10124, 2009 4363, 01KW9977/0, CA116201, 193387/H10, NKI 2007–3839, DDHK 2009‐4318, CA58860, RUL1997-1505, CA92044, 01KW0114, 39346, 209057, 110837, C1287/A10118, 01KW9975/5, BBMRI-NL CP16)
Leids Universitair Medisch Centrum
Universitetet i Oslo (209057)
Norges Forskningsråd (01KW0114, 209057, BBMRI-NL CP16, 193387/H10, 2007-3839, C1287/A10118, 01KW9975/5, 110837, 2009 4363, RUL 1997-1505, 01KW9976/8, CA58860, PBZ_KBN_122/P05/2004, DDHK 2004-3124, CA116201, UM1 CA164920, C490/A10124, LVS39420, 39346, 193387/V50, 01KW9977/0, RUS08/017, HEALTH-F2-2009-223175, CA92044, DDHK 2009-4318, 70492)
Medizinischen Hochschule Hannover (01KW0114, 2007-3839, 39346, 2009 4363, DDHK 2004-3124, 209057, 193387/H10, C1287/A10118, 01KW9976/8, 01KW9975/5, 193387/V50, 110837, RUL 1997-1505, RUS08/017, C490/A10124, BBMRI-NL CP16, CA92044, CA58860, DDHK 2009-4318, CA116201, LVS39420, 70492, HEALTH-F2-2009-223175, PBZ_KBN_122/P05/2004, 01KW9977/0, UM1 CA164920)
Technische Universität München
Deutsche Krebshilfe (HEALTH-F2-2009-223175, 193387/H10, (#110837, 2007-3839, 01KW0114, DDHK 2004-3124, CA58860, RUL 1997-1505, UM1 CA164920, 01KW9976/8, C490/A10124, DDHK 2009-4318, CA92044, 209057, PBZ_KBN_122/P05/2004, 01KW9977/0, BBMRI-NL CP16, 01KW9975/5, 39346, CA116201, 2009 4363, C1287/A10118, 70492, 193387/V50, LVS39420, RUS08/017)
Universität zu Köln
Pomorski Uniwersytet Medyczny W Szczecinie
Universitätsklinikum Köln
National Institutes of Health (LVS39420, CA11620 1, DDHK 2009-4318, 01KW0114, 01KW9977/0, 01KW9975/5, 223175, 39346, 184.021.007, 193387/V50, 2007-3839, RUL 1997-1505, 193387/H10, 110837, 70492, C490/A10124, PBZ_KBN_122/P05/2004, RUS08/017, 01KW9976/8, C1287/A10118, BBMRI-NL CP16, 209057, HEALTH-F2-2009-223175, 3u01ca164920-07s1, DDHK 2004-3124, 2009 4363, CA116167, CA164920, CA58860)
School of Medicine, Stanford University
U.S. Army (DAMD17-01-1-0729)
University of California, Los Angeles
University of California, Irvine
Medical Research Council (110837, CA58860, 70492, CA116201, PBZ_KBN_122/P05/2004, RUL 1997-1505, DDHK 2004-3124, RUS08/017, MC_PC_14105, BBMRI-NL CP16, HEALTH-F2-2009-223175, UM1 CA164920, 01KW9975/5, 01KW9976/8, 193387/V50, 01KW0114, 193387/H10, 2009 4363, 2007-3839, C490/A10124, C1287/A10118, CA92044, 39346, 209057, LVS39420, 01KW9977/0, DDHK 2009-4318)
National Health and Medical Research Council (251553, 199600, 400281, 209057, 400413, 400281, 400413, 504711)
Cancer Council South Australia
Cancer Council Victoria (DDHK 2004-3124, UM1 CA164920, 110837, C1287/A10118, CA92044, 39346, 209057, HEALTH-F2-2009-223175, 2007-3839, CA116201, 193387/V50, 01KW9976/8, 01KW0114, DDHK 2009-4318, C490/A10124, PBZ_KBN_122/P05/2004, CA58860, 2009 4363, RUS08/017, RUL 1997-1505, BBMRI-NL CP16, 01KW9977/0, 01KW9975/5, 70492, LVS39420, 193387/H10)
Cancer Council NSW
Cancer Council Tasmania
Russian Academy of Sciences
Erasmus Universitair Medisch Centrum Rotterdam
Universitätsklinikum Hamburg-Eppendorf
National Cancer Institute (01KW9976/8, RUS08/017, PBZ_KBN_122/P05/2004, U01CA058860, HEALTH-F2-2009-223175, CA116167, DDHK 2009-4318, R01CA058860, 01KW9975/5, R01CA116167, UM1CA164920, 193387/H10, R01CA069664, R01CA047305, RUL 1997-1505, CA-116201, 2009 4363, R01CA192393, 209057, CA164920, CA58860, 01KW9977/0, 2007-3839, 193387/V50, 39346, CA176785, 01KW0114, K07CA092044, CA192393, C1287/A10118, 110837, DAMD17-01-1-0729, U01CA116167, DDHK 2004-3124, BBMRI-NL-CP16, R01CA176785, C490/A10124, CA92044, R01CA047147, 70492, P30CA008748, P50CA116201, LVS39420)
David Geffen School of Medicine, University of California, Los Angeles
Medical Research and Materiel Command (DAMD17-01–1-0729)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: CHEK2 1100delC, germline mutation carriers, breast cancer risk, tumor subtypes, estrogen receptor-positive breast cancer, age-specific risk, cumulative risk, breast cancer risk prediction, Breast Cancer Association Consortium, hereditary breast cancer, odds ratio, heterozygous carriers
MeSH terms: Adult, Age Factors, Aged, Aged, 80 and over, Breast Neoplasms, Female, Heterozygote, Homozygote, Humans, Middle Aged, Receptors, Estrogen, Receptors, Progesterone, Odds Ratio, Case-Control Studies, Sequence Deletion, Risk Assessment, Genetic Predisposition to Disease, Checkpoint Kinase 2

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Age- and Tumor Subtype–Specific Breast Cancer Risk Estimates for CH EK 2 *1100delC Carriers

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