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 me 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.
Original language | English |
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Pages (from-to) | 53-65 |
Number of pages | 13 |
Journal | Disease Markers |
Volume | 15 |
Publication status | Published - 1999 |
Keywords
- genetic counselling
- genetic risk assessment
- familial breast cancer
- OVARIAN-CANCER
- LINKAGE ANALYSIS
- FAMILY HISTORY
- BRCA2 MUTATION
- COMMON BRCA1
- POPULATION
- FREQUENCY
- CARRIERS
- HETEROGENEITY
- INDIVIDUALS