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.

Additional Metadata
Keywords Breast cancer, CHEK2, CHEK2*1100delC, Cancer incidence, Familial, Relatives
Persistent URL dx.doi.org/10.1016/j.ejca.2013.01.009, hdl.handle.net/1765/40105
Journal European Journal of Cancer
Citation
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