BRCA 1, BRCA 2 models.

Anticipating that genetic tests designed to determine an individuals predisposition to disease would eventually become commercially available, and recognizing that the results of many of these tests may have mortality implications, in 1994 Lincoln National Reinsurance Companies began developing a methodology that would allow the mortality risk associated with a number of different genetic mutations to be modeled. Because we felt that recent discoveries concerning the BRCA1 gene made it likely that tests for this gene would soon be available commercially, we selected BRCA1 mutations as the first to model. BRCA1 is one of a number of tumor surpresser genes, which, if mutated, may result in the production of a defective "tumor suppressor protein" and the development of a cancer. BRCA1 was first identified in 1990 by Hall et al. and localized to chromosome 17q. At first, BRCA1 was characterized as a breast cancer predisposition gene. Since then, investigators have determined that BRCA1 mutations result in predispositions not only to breast cancer but also to ovarian and, to a slight extent, pro.state and colon cancers. In papers published in 1993 and 1994, Easton et al. devised models to estimate the risk of breast and ovarian cancer using linkage analysis data collected by the Breast Cancer Linkage Consortium. From their models, they concluded that the risk of developing breast cancer due to BRCA1 mutations was best described by