title: BRCA1, BRCA2 and CHEK2 c.1100 delC mutations in patients with double primaries of the breasts and/or ovaries.
abstract: BACKGROUND
  Previous publications and utilisation of risk models for BRCA1 and BRCA2 mutation identification suggests that multiple primary disease in an individual is a strong predictor of a BRCA1/2 mutation and that this is more predictive than the same cancers occurring in close relatives.
  
  
  METHODS
  This study assessed the pathological mutation detection rates for BRCA1, BRCA2 and the CHEK2c.1100 delC mutation in 2022 women with breast cancer, including 100 with breast/ovary double primary and 255 with bilateral breast cancer.
  
  
  CONCLUSIONS
  Although detection rates for mutations in BRCA1/2 are high at 49% for breast/ovarian double primary and 34% for bilateral breast cancer, the differential effect of multiple primaries in an individual appears to have been overestimated, particularly in those families with only a few malignancies. Nonetheless, bilateral breast cancer does differentially enhance detection rates in strong familial aggregations. CHEK2 1100 DelC mutation rates were lower in bilateral than for unilateral cases at 0.8% compared to 2%. The detected mutation rates for isolated double primary breast and ovarian cancer was 14% (3/22) compared to 17% (17/99) for the same two primaries in two close relatives in families with no other cases of breast/ovarian cancer. Risk models may need to be adjusted if further studies corroborate these findings.
authors.affiliation: Genetic Medicine, St Mary's Hospital, Manchester Academic Health Science Centre, Central Manchester University Hospitals Foundation Trust, Manchester, UK. gareth.evans@cmft.nhs.uk
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Munaza
authors.initials: M
authors.lastname: Ahmed
authors.forename: Stuart
authors.initials: S
authors.lastname: Bayliss
authors.forename: Emma
authors.initials: E
authors.lastname: Howard
authors.forename: Fiona
authors.initials: F
authors.lastname: Lalloo
authors.forename: Andrew
authors.initials: A
authors.lastname: Wallace
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D064447:Checkpoint Kinase 2; D005190:Family; D005260:Female; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000201:enzymology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases