Hereditary cancers: from discovery to intervention.

This conference concerned hereditary cancers of the breast, ovary, and colon, which are the common, often fatal, cancers with the greatest heritability in their causation. Four genes whose mutations impart dominantly heritable predisposition to one or more of these cancers have been cloned and one more has been mapped. The most molecular details are known for colon cancer. The APC gene of familial polyposis coli leads to the accumulation of numerous polyps, but the probability of transformation of the latter to cancer is low. This provides the opportunity to monitor putative preventive measures with an intermediate end point. In hereditary nonpolyposis colon cancer, transformation of the polyp to cancer is accelerated by an inherited mutation in either of two DNA mismatch repair genes. The discovery of an intermediate end point could be very helpful for breast cancer. Testing persons at risk for predisposing mutations depends heavily on the availability of promising measures for prevention or treatment.