Aim: The CHEK2*1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2*1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Patients and Methods: Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2*1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2*1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n = 2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2*1100delC status of relatives was unknown. Results: Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4-2.7), p < 0.001) was observed in sisters of CHEK2*1100delC positive index cases compared to sisters of CHEK2*1100delC negative index cases. HR was 1.6 (95% CI: 1.0-2.4) for mothers of CHEK2 positive versus negative index cases (p = 0.041). For second primary breast cancers HR was increased in CHEK2*1100delC positive index cases (HR 2.1, 95% CI: 1.3-3.3, p = 0.003) and their sisters (HR 2.6, 95% CI: 1.1-6.1, p = 0.025). Conclusion: There is an excess breast cancer risk in first degree relatives of CHEK2*1100delC positive non-BRCA1/2 familial breast cancer patients compared to non-CHEK2*1100delC familial breast cancer relatives. Genotyping for the CHEK2*1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs.

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Keywords Breast cancer, CHEK2, CHEK2*1100delC, Cancer incidence, Familial, Relatives
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Journal European Journal of Cancer
Adank, M.A, Verhoef, S, Oldenburg, R.A, Schmidt, M.K, Hooning, M.J, Martens, J.W.M, … Meijers-Heijboer, E.J. (2013). Excess breast cancer risk in first degree relatives of CHEK2* 1100delC positive familial breast cancer cases. European Journal of Cancer, 49(8), 1993–1999. doi:10.1016/j.ejca.2013.01.009