title: No evidence of increased breast cancer risk for proven noncarriers from BRCA1 and BRCA2 families.
abstract: In families screened for mutations in the BRCA1 or BRCA2 genes and found to have a segregating mutation the breast cancer risk for women shown not to carry the family-specific mutation might be at above "average" risk. We assessed the risk of breast cancer in a clinic based cohort of 725 female proven noncarriers in 239 BRCA1 and BRCA2 families compared with birth-matched controls from the Danish Civil Registration System. Prospective analysis showed no significantly increased risk for breast cancer in noncarriers with a hazard ratio of 0.67 [95 % confidence interval (CI) 0.32-1.42, p = 0.29] for all family members who tested negative and 0.87 (95 % CI 0.38-1.97, p = 0.73) for non-carries who were first-degree relatives of mutation carriers. Proven noncarriers from BRCA1 and BRCA2 families have no markedly increased risk for breast cancer compared to the general population, and our data do not suggest targeted breast cancer surveillance for noncarriers from BRCA1 and BRCA2 families.
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100, Vejle, Denmark. henriette.roed.nielsen@rsyd.dk.
authors.forename: Henriette Roed
authors.initials: HR
authors.lastname: Nielsen
authors.affiliation: HNPCC Register, Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark.|Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Janne
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Krogh
authors.affiliation: HNPCC Register, Clinical Research Center, Copenhagen University Hospital, Hvidovre, Denmark.|Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
authors.affiliation: Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne-Bine
authors.initials: AB
authors.lastname: Skytte
mesh_terms: D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: Female cancer risk; HBOC; Hereditary cancer; Modifiers; Phenocopies