Age- and tumor subtype- Specific breast cancer risk estimates for CHEK2∗1100delC carriers Journal Article

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.
Article Title: Age- and tumor subtype- Specific breast cancer risk estimates for CHEK2∗1100delC carriers
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. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 23
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-08-10
Start Page: 2750
End Page: 2760
Language: English
DOI: 10.1200/jco.2016.66.5844
PROVIDER: scopus
PUBMED: 27269948
PMCID: PMC5019754
Notes: Article -- Export Date: 1 September 2016 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    495 Offit
  2. Mark E Robson
    358 Robson