Family History in Risk Assessment

Family history is clearly of great importance in diagnosis and risk assessment. Applying the known rules of mendelian inheritance, as introduced in Chapter 7, allows the geneticist to provide accurate evaluations of risk for disease in relatives of affected individuals. Family history is also important when a geneticist assesses the risk for complex disorders, as discussed in Chapter 8 and elsewhere in this book. Because a person’s genes are shared with his or her relatives, family history provides the clinician with information on the impact that an individual’s genetic makeup might have on one’s health, using the medical history of relatives as an indicator of one’s own genetic susceptibilities. Furthermore, family members often share environmental factors, such as diet and behavior, and thus relatives provide information about both shared genes and shared environmental factors that may interact to cause the common, genetically complex diseases. Having a first-degree relative with a common disease of adulthood—such as cardiovascular disease, cancer of the breast, cancer of the colon or prostate, type 2 diabetes, osteoporosis, or asthma—raises an individual’s risk for the disease approximately twofold to threefold relative to the general population, a moderate increase compared with the average population risk (see Box). As discussed in Chapter 8, the more first-degree relatives one has with a complex trait and the earlier in life the disease occurs in a family member, the greater the load of susceptibility genes and environmental exposures likely to be present in the patient’s family. Thus consideration of family history can lead to the designation of a patient as being at high risk for a particular disease on the basis of family history. For example, a male with three male first-degree relatives with prostate cancer has an 11-fold greater relative risk for development of the disease than does a man with no such family history.