title: German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer.
abstract: CHEK2*1100delC 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 CHEK2*1100delC 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. CHEK2*1100delC 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 CHEK2*1100delC 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 CHEK2*1100delC 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 CHEK2*1100delC 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.
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, B055, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Muhammad U
authors.initials: MU
authors.lastname: Rashid
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Christina
authors.initials: C
authors.lastname: Justenhoven
authors.forename: Volker
authors.initials: V
authors.lastname: Harth
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Christian
authors.initials: C
authors.lastname: Baisch
authors.forename: Christiane B
authors.initials: CB
authors.lastname: Pierl
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
authors.forename: Yon
authors.initials: Y
authors.lastname: Ko
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Heinz-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005838:Genotype; D005858:Germany; D006801:Humans; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases