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

Schmidt MK, Hogervorst F, Van Hien R, Cornelissen S, Broeks A, Adank MA, Meijers H, Waisfisz Q, Hollestelle A, Schutte M, Van Den Ouweland A, Hooning M, Andrulis IL, Anton-Culver H, Antonenkova NN, Antoniou AC, Arndt V, Bermisheva M, Bogdanova NV, Bolla MK, Brauch H, Brenner H, Bruning T, Burwinkel B, Chang-Claude J, Chenevix-Trench G, Couch FJ, Cox A, Cross SS, Czene K, Dunning AM, Fasching P, Figueroa J, Fletcher O, Flyger H, Galle E, Garcia-Closas M, Giles GG, Häberle L, Hall P, Hillemanns P, Hopper JL, Jakubowska A, John EM, Jones M, Khusnutdinova E, Knight JA, Kosma VM, Kristensen V, Lee A, Lindblom A, Lubinski J, Mannermaa A, Margolin S, Meindl A, Milne RL, Muranen TA, Newcomb PA, Offit K, Park-Simon TW, Peto J, Pharoah PDP, Robson M, Rudolph A, Sawyer EJ, Schmutzler RK, Seynaeve C, Soens J, Southey MC, Spurdle AB, Surowy H, Swerdlow A, Tollenaar RAEM, Tomlinson I, Trentham-Dietz A, Vachon C, Wang Q, Whittemore AS, Ziogas A, Van Der Kolk L, Nevanlinna H, Doerk T, Bojesen S, Easton DF (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 34

Pages Range: 2750-60

Journal Issue: 23

DOI: 10.1200/JCO.2016.66.5844

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.

Authors with CRIS profile

Involved external institutions

Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Karolinska Institute SE Sweden (SE) University of Sheffield GB United Kingdom (GB) University of Eastern Finland FI Finland (FI) Vrije Universiteit Amsterdam (VU) / University Amsterdam NL Netherlands (NL) Antoni van Leeuwenhoek NL Netherlands (NL) Erasmus University Medical Center (MC) NL Netherlands (NL) University of Edinburgh GB United Kingdom (GB) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) RU Russian Federation (RU) University of Cambridge GB United Kingdom (GB) The University of Melbourne AU Australia (AU) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Mount Sinai Hospital (MSH) CA Canada (CA) University of Wisconsin - Madison US United States (USA) (US) King’s College London GB United Kingdom (GB) Helsingin yliopisto / University of Helsinki FI Finland (FI) Ruhr-Universität Bochum (RUB) DE Germany (DE) Memorial Sloan Kettering Cancer Center US United States (USA) (US) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven BE Belgium (BE) Universitätsklinikum Köln DE Germany (DE) University of Oxford GB United Kingdom (GB) Copenhagen University Hospital DK Denmark (DK) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) University of California Irvine US United States (USA) (US) Stanford University US United States (USA) (US) Cancer Council Victoria AU Australia (AU) Bashkir State University / Башкирский государственный университет RU Russian Federation (RU) Mayo Clinic US United States (USA) (US) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology BY Belarus (BY) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) PL Poland (PL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO) Cancer Prevention Institute of California (CPIC) US United States (USA) (US) National Cancer Institute (NCI) US United States (USA) (US) Technische Universität München (TUM) DE Germany (DE) Leiden University NL Netherlands (NL)

How to cite

APA:

Schmidt, M.K., Hogervorst, F., Van Hien, R., Cornelissen, S., Broeks, A., Adank, M.A.,... Easton, D.F. (2016). Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. Journal of Clinical Oncology, 34(23), 2750-60. https://dx.doi.org/10.1200/JCO.2016.66.5844

MLA:

Schmidt, Marjanka K., et al. "Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers." Journal of Clinical Oncology 34.23 (2016): 2750-60.

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