Estimating disease risks for individuals with a given family history in different populations with an application to breast cancer.

For many chronic diseases, including most of the common cancers, a family history is known to be a strong independent risk factor. For breast cancer, estimation of risk as a function of family history is considered to provide useful risk assessment for women with a family history of breast cancer. Detailed tables that predict the cumulative risk of breast cancer at specific ages based on various combinations of family history have been constructed for the American white population. Most chronic diseases, however, have a multiple etiology, with multiple genetic and environmental factors. Family history can thus be a result of different susceptibility loci and the aggregation of sporadic cases by chance. Since the relative contribution of the genetic factor may differ in different populations, these tables may not be directly applicable to other populations. We present a method to decompose available estimates of risk based on family history for an arbitrary disease into probabilities for genotype frequency given a particular family history and for disease probabilities by genotype carrier status. These can be reconstructed to obtain risk estimates for different populations. Implicit assumptions are made in the estimation process. These are based on the current state of knowledge and can be updated as further knowledge accumulates.