Age-And tumor subtype-specific breast cancer risk estimates for CHEK2∗1100delC Carriers

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

Research output: Contribution to journalArticle

70 Scopus citations

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 subtypeand 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 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 3 10-21]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 3 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.

Original languageEnglish (US)
Pages (from-to)2750-2760
Number of pages11
JournalJournal of Clinical Oncology
Volume34
Issue number23
DOIs
StatePublished - Aug 10 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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., ... Easton, D. F. (2016). Age-And tumor subtype-specific breast cancer risk estimates for CHEK2∗1100delC Carriers. Journal of Clinical Oncology, 34(23), 2750-2760. https://doi.org/10.1200/JCO.2016.66.5844