title: Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Genetics, VU University Medical Center, P.O. Box 7057, 1081 HV Amsterdam, The Netherlands.
authors: Muriel A
authors: MA
authors: Adank
authors: Senno
authors: S
authors: Verhoef
authors: Rogier A
authors: RA
authors: Oldenburg
authors: Marjanka K
authors: MK
authors: Schmidt
authors: Maartje J
authors: MJ
authors: Hooning
authors: John W M
authors: JW
authors: Martens
authors: Annegien
authors: A
authors: Broeks
authors: Matti
authors: M
authors: Rookus
authors: Quinten
authors: Q
authors: Waisfisz
authors: Birgit I
authors: BI
authors: Witte
authors: Marianne A
authors: MA
authors: Jonker
authors: Hanne
authors: H
authors: Meijers-Heijboer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005190:Family; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D035781:Siblings
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases