The human genome project and the discovery of genetic determinants of cancer susceptibility

The Human Genome Project has recently provided a great deal of information on the sequence that comprises the human genome. We are now in the process of structuring and deciphering the 3 × 109 base sequence in order to gain insights into its functional role. Several efforts are focusing on the search for DNA sequence variations underlying common/complex diseases that constitute a real burden in terms of public health measures. As expected, the genetic architecture of these complex traits, shows tremendous complexity, and the discovery and characterisation of susceptibility alleles constitute a real challenge for the geneticist. Conceptual and experimental genetic approaches aimed at dissecting the molecular features of susceptibility genes, in particular those predisposing to cancer, are outlined and discussed in this reveiw.