A family history of breast cancer has long been recognized to be associated with predisposition to the disease, but only recently have susceptibility genes, BRCA1 and BRCA2, been identified. Though rare, mutation of a gene at either locus is associated with a much increased risk of developing breast as well as ovarian cancer. Understanding this risk is an important element of medical counseling in clinics that serve women who present with a family history. In this paper we discuss validation of a probability model for risk of mutation at BRCA1 or BRCA2.
Genetic status is unknown, but of interest, for a sample of individuals.
Family histories of breast and ovarian cancer in First and Second degree relatives are available and enable calculation, via the mode of Berry, et al. 1997 and Parmigiani, et al. 1998, of a carrier probability score. Results of genetic tests with unknown error rates are available with which to validate carrier probability scores. A model is developed which allows joint assessment of test sensitivity and specificity and carrier score error, treating genetic status as a latent variable. We gratefully acknowledge Elaine Hiller and Judy Garber of the Dana Farber Cancer Institute for providing us with pedigrees for the 121 genetically tested individuals used here.