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.

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Persistent URL dx.doi.org/10.1200/JCO.2016.66.5844, hdl.handle.net/1765/96730
Journal Journal of Clinical Oncology
Schmidt, M.K, Hogervorst, F.B.L, van Hien, R.R, Cornelissen, S. (Sten), 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), 2750–2760. doi:10.1200/JCO.2016.66.5844