Heritable colorectal cancer and cancer genes: systemic expressions.

Epidemiological studies of heritable cancer have demonstrated that cancer predisposition is a dominant trait; these studies have also predicted the recessive outcome of the neoplastic process. Biochemical studies of dominantly heritable cancer have demonstrated the relevance of systemic effects. The systemic effects are presumably due to a dominant mutation at the "initiator locus." Collectively they define cancer initiation at the cellular level (as described in this review). Molecular biological studies have demonstrated that cancer progression and the appearance of clinical cancer occur through an accumulation of recessive mutations at critical loci. We must continue to try to define not only the inherited and acquired gene defects that initiate the neoplastic state but also the subsequent genetic alterations and biomarkers involved in tumor progression. These genetic defects are already proving useful in diagnosis and prognostication. The hope is that these biomarkers may be useful for designing specific differentiation therapy.