title: CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women.
abstract: BACKGROUND
  Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors. This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk.
  
  
  RESULTS
  Homozygosity for the CHEK2*1100delC allele was identified in 8/2554 Dutch independent familial non-BRCA1/2 breast cancer cases. The genotype relative risk for breast cancer of homozygous and heterozygous familial breast cancer cases was 101.34 (95% CI 4.47 to 121 000) and 4.04 (95% CI 0.88 to 21.0), respectively. Female homozygotes appeared to have a greater than twofold increased breast cancer risk compared to familial CHEK2*1100delC heterozygotes (p=0.044). These results and the occurrence of multiple primary tumours in 7/10 homozygotes indicate a high cancer risk in homozygous women from non-BRCA1/2 families.
  
  
  CONCLUSIONS
  Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non-BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2.
authors: Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands.
authors: Muriel A
authors: MA
authors: Adank
authors: Marianne A
authors: MA
authors: Jonker
authors: Irma
authors: I
authors: Kluijt
authors: Saskia E
authors: SE
authors: van Mil
authors: Rogier A
authors: RA
authors: Oldenburg
authors: Wolter J
authors: WJ
authors: Mooi
authors: Frans B L
authors: FB
authors: Hogervorst
authors: Ans M W
authors: AM
authors: van den Ouweland
authors: Johan J P
authors: JJ
authors: Gille
authors: Marjanka K
authors: MK
authors: Schmidt
authors: Aad W
authors: AW
authors: van der Vaart
authors: Hanne
authors: H
authors: Meijers-Heijboer
authors: Quinten
authors: Q
authors: Waisfisz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D064447:Checkpoint Kinase 2; D005260:Female; D016368:Frameshift Mutation; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases