title: Age at diagnosis as an indicator of eligibility for BRCA1 DNA testing in familial breast cancer.
abstract: We searched for criteria that could indicate breast cancer families with a high prior probability of being caused by the breast/ovarian cancer susceptibility locus BRCA1 on chromosome 17. To this end, we performed a linkage study with 59 consecutively collected Dutch breast cancer families, including 16 with at least one case of ovarian cancer. We used an intake cut-off of at least three first-degree relatives with breast and/or ovarian cancer at any age. Significant evidence for linkage was found only among the 13 breast cancer families with a mean age at diagnosis of less than 45 years. An unexpectedly low proportion of the breast-ovarian cancer families were estimated to be linked to BRCA1, which could be due to a founder effect in the Dutch population. Given the expected logistical problems in clinical management now that BRCA1 has been identified, we propose an interim period in which only families with a strong positive family history for early onset breast and/or ovarian cancer will be offered BRCA1 mutation testing.
authors.affiliation: Department of Human Genetics, University of Leiden, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Cornelis
authors.forename: H F
authors.initials: HF
authors.lastname: Vasen
authors.forename: H
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: D
authors.initials: D
authors.lastname: Ford
authors.forename: M
authors.initials: M
authors.lastname: van Vliet
authors.forename: A A
authors.initials: AA
authors.lastname: van Tilborg
authors.forename: F J
authors.initials: FJ
authors.lastname: Cleton
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
authors.forename: F H
authors.initials: FH
authors.lastname: Menko
authors.forename: P
authors.initials: P
authors.lastname: Meera Khan
mesh_terms: D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D014157:Transcription Factors