The BOADICEA model of genetic susceptibility to breast and ovarian cancer

摘要

Several genes conferring susceptibility to breast and ovarian cancer, notably BRCA1 and BRCA2, have been identified. The majority of the familial aggregation of breast cancer is, however, not explained by these genes. We have previously derived, using segregation analysis, a susceptibility model (BOADICEA, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) in which susceptibility to these genes is explained by mutations in BRCA1 and BRCA2 together with a polygenic component reflecting the joint multiplicative effect of multiple genes of small effect on breast cancer risk. Here, we consider the predictions made by this model. The overall familial risks of breast cancer predicted by this model are close to those observed in epidemiological studies. The predicted prevalences of BRCA1 and BRCA2 mutations among unselected cases of breast and ovarian cancer are also consistent with observations from population-based studies. These predictions are closer to the observed values than those obtained using the Claus model and BRCAPRO. The predicted mutation probabilities and cancer risks in individuals with a family history (FH) can differ markedly from those predicted by other models. We conclude that this model provides a rational basis for risk assessment in individuals with a FH of breast or ovarian cancer.