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J Clin Oncol. 2016 Aug 10;34(23):2750-60. doi: 10.1200/JCO.2016.66.5844. Epub 2016 Jun 6.

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

Author information

1
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, Leiden, the Netherlands; Irene L. Andrulis and Julia A. Knight, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital; Irene L. Andrulis and Julia A. Knight, University of Toronto, Toronto, Ontario, Canada; Hoda Anton-Culver and Argyrios Ziogas, University of California, Irvine; Peter A. Fasching, David Geffen School of Medicine, University of California, Los Angeles; Esther M. John, Cancer Prevention Institute of California, Fremont; Esther M. John, Alice S. Whittemore, Stanford University School of Medicine, Stanford, CA; Natalia N. Antonenkova, N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus; Antonis C. Antoniou, Manjeet K. Bolla, Andrew Lee, Alison M. Dunning, Paul D.P. Pharoah, Qin Wang, and Douglas F. Easton, University of Cambridge, Cambridge; Angela Cox and Simon S. Cross, University of Sheffield, Sheffield; Olivia Fletcher, Michael Jones, and Anthony Swerdlow, The Institute of Cancer Research; Julian Peto, London School of Hygiene and Tropical Medicine; Elinor J. Sawyer, King's College London, London; Jonine Figueroa, University of Edinburgh Medical School, Edinburgh; Ian Tomlinson, University of Oxford, Oxford, United Kingdom; Volker Arndt, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Jenny Chang-Claude, Anja Rudolph, Harold Surowy, German Cancer Research Center; Barbara Burwinkel and Harald Surowy, University of Heidelberg, Heidelberg; Natalia V. Bogdanova, Peter Hillemanns, Tjoung-Won Park-Simon, and Thilo

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.

PMID:
27269948
PMCID:
PMC5019754
DOI:
10.1200/JCO.2016.66.5844
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

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