title: Risk estimation as a decision-making tool for genetic analysis of the breast cancer susceptibility genes. EC Demonstration Project on Familial Breast Cancer.
abstract: For genetic counselling of a woman on familial breast cancer, an accurate evaluation of the probability that she carries a germ-line mutation is needed to assist in making decisions about genetic-testing. We used data from eight collaborating centres comprising 618 families (346 breast cancer only, 239 breast or ovarian cancer) recruited as research families or counselled for familial breast cancer, representing a broad range of family structures. Screening was performed in affected women from 618 families for germ-line mutations in BRCA1 and in 176 families for BRCA2 mutations, using different methods including SSCP, CSGE, DGGE, FAMA and PTT analysis followed by direct sequencing. Germ-line BRCA1 mutations were detected in 132 families and BRCA2 mutations in 16 families. The probability of being a carrier of a dominant breast cancer gene was calculated for the screened individual under the established genetic model for breast cancer susceptibility, first, with parameters for age-specific penetrances for breast cancer only [7] and, second, with age-specific penetrances for ovarian cancer in addition [20]. Our results indicate that the estimated probability of carrying a dominant breast cancer gene gives a direct measure of the likelihood of detecting mutations in BRCA1 and BRCA2. For breast/ovarian cancer families, the genetic model according to Narod et al. [20] is preferable for calculating the proband's genetic risk, and gives detection rates that indicate a 50% sensitivity of the gene test. Due to the incomplete BRCA2 screening of the families, we cannot yet draw any conclusions with respect to the breast cancer only families.
authors.affiliation: Deutsches Krebsforschungszentrum, Division of Epidemiology, Heidelberg, Germany. claude@dkfz-heidelberg.de
authors.forename: J
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: H
authors.initials: H
authors.lastname: Becher
authors.forename: M
authors.initials: M
authors.lastname: Caligo
authors.forename: D
authors.initials: D
authors.lastname: Eccles
authors.forename: G
authors.initials: G
authors.lastname: Evans
authors.forename: N
authors.initials: N
authors.lastname: Haites
authors.forename: S
authors.initials: S
authors.lastname: Hodgson
authors.forename: P
authors.initials: P
authors.lastname: Møller
authors.forename: B H
authors.initials: BH
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D003657:Decision Making; D003661:Decision Support Techniques; D005060:Europe / Q000453:epidemiology; D005260:Female; D019398:Genes, BRCA1; D005799:Genes, Dominant; D005817:Genetic Counseling / Q000379:methods*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009363:Neoplasm Proteins / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics*; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics; D011237:Predictive Value of Tests; D011336:Probability; D012306:Risk; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors