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Disease Markers
Volume 15, Issue 1-3, Pages 53-65

Risk Estimation as a Decision-Making Tool for Genetic Analysis of the Breast Cancer Susceptibility Genes

Jenny Chang-Claude,1 Heiko Becher,1 Maria Caligo,2 Diana Eccles,3 Gareth Evans,4 Neva Haites,5 Shirley Hodgson,6 Pål Møller,7 Bernhard H. F. Weber,8 and Dominique Stoppa-Lyonnet9

1Deutsches Krebsforschungszentrum, Division of Epidemiology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
2Department of Oncology, University of Pisa, via Roma 57, 56126 Pisa, Italy
3Wessex Clinical Genetic Services, Princess Ann Hospital, Coxford Road, Southampton SO16 5YA, UK
4Clinical Genetic Services, St. Mary’s Hospital, Oxford Road, Manchester M13 0JH, UK
5Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, AB25 2ZD, UK
6Genetics Centre, Guy’s Hospital, St. Thomas Street, London SE1 9RT, UK
7Unit of Medical Genetics, The Norwegian Radium Hospital, 0310 Oslo, Norway
8Institut für Humangenetik, 97074 Würzburg, Germany
9Service de Génétique Oncologique, Institut Curie, rue d’Ulm 26, 75231 Paris, France

Received 9 December 1999; Accepted 9 December 1999

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.