Genetic Predisposition to Cancer

ABSTRACT Evidence of genetic predisposition has to come from specialized investigations of biologically meaningful groups within populations. Such investigations have provided ample and convincing evidence of a genetic basis for virtually all of the major cancer types and sites. However, this should not be construed to mean that all cancers at a given site or of a given type involve an inherited basis; rather, such a basis only applies to a certain fraction of patients. The occurrence of inherited and non-inherited cancers accords with a two-step mutation model, the first of which may be inherited or spontaneous and the second may be spontaneous or induced by environmental mutagens. When the first of these mutations is inherited, the number of subsequent mutations necessary for tumor production is thus reduced and gene carriers are uniquely sensitive to exposure to environmental mutagens. Subsequent tumor development will occur at an earlier than average age and will also develop at multiple sites. Evidence is thus accumulating pointing to the importance of an environmental component in the development of cancer in genetically susceptible individuals.