German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer.

CHEK21100delC is associated with a twofold increased breast cancer risk. This was shown in a collaborative analysis of European populations, but not in other populations from Europe and the US. Accordingly, there is a need to clarify the role of CHEK21100delC in breast cancer. We established its prevalence in two German populations GENICA (Northrhine-Westphalia, n = 724) and KORA (Bavaria, n = 600) and in women with breast cancer. The latter included cases (n = 688) from the GENICA breast cancer case-control study, patients with early-onset breast cancer (n = 86) and patients with familial breast cancer (n = 71). The latter patient groups were previously investigated for BRCA1/2-mutations and tested negative. Mutation analysis was performed by combined PCR/DHPLC methodology. CHEK21100delC was found in 0.9% of GENICA controls and was absent in the KORA controls indicating a significant difference between the two populations (P= 0.03). The frequency of CHEK21100delC in age-matched cases of the GENICA collection was 0.8% and thus not different from controls (OR 0.88, 95% CI 0.21-3.50). In patients with early-onset disease CHEK21100delC was found at a frequency of 2.3% referring to an increased breast cancer risk of 2.56 (95% CI 0.25-14.58). In patients with familial disease the frequency was 1.4% referring to an increased risk of 1.53 (95% CI 0.03-12.93). Our data showed variations in CHEK21100delC prevalence within German populations suggesting possible inaccuracies in breast cancer risk assessments from non population-based studies. In patients with a high-risk profile however, CHEK2*1100delC was indicative for this risk and highest for early-onset breast cancer.