title: Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.
abstract: OBJECTIVE
  To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer.
  
  
  METHODS
  Seven thousand four hundred ninety-four BRCA1 mutation-negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T).
  
  
  RESULTS
  A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both a first- and second-degree relative affected.
  
  
  CONCLUSIONS
  CHEK2 mutation screening detects a clinically meaningful risk of breast cancer and should be considered in all women with a family history of breast cancer. Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul. Połabska 4, 70-115 Szczecin, Poland. cezarycy@sci.pam.szczecin.pl
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Dominika
authors.initials: D
authors.lastname: Wokołorczyk
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Masojć
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Deebniak
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Paweł
authors.initials: P
authors.lastname: Blecharz
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases