Schmidt, MK; Hogervorst, F; van Hien, R; Cornelissen, S; Broeks, A; Adank, MA; Meijers, H; Waisfisz, Q; Hollestelle, A; Schutte, M; +74 more... 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; Brüning, T; Burwinkel, B; Chang-Claude, J; Chenevix-Trench, G; Couch, FJ; Cox, A; Cross, SS; Czene, K; Dunning, AM; Fasching, PA; Figueroa, J; Fletcher, O; Flyger, H; Galle, E; García-Closas, M; Giles, GG; Haeberle, 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, PD; Robson, M; Rudolph, A; Sawyer, EJ; Schmutzler, RK; Seynaeve, C; Soens, J; Southey, MC; Spurdle, AB; Surowy, H; Swerdlow, A; Tollenaar, RA; Tomlinson, I; Trentham-Dietz, A; Vachon, C; Wang, Q; Whittemore, AS; Ziogas, A; van der Kolk, L; Nevanlinna, H; Dörk, T; Bojesen, S; Easton, DF; (2016) Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. Journal of clinical oncology. ISSN 0732-183X DOI: https://doi.org/10.1200/JCO.2016.66.5844
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Abstract
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. 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. 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. 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.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
PubMed ID | 27269948 |
ISI | 382467000012 |
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