Detecting low penetrance genes in cancer: the way ahead

The search for the genes responsible for many complex genetic diseases is w ell under way and has already been successful in some cases. The study of c ancer as a complex genetic disease has lagged behind other conditions, larg ely because of particular problems that are associated with malignant disea se. Cancer also, however, presents specific opportunities for gene identifi cation, which are not found in many other diseases. While the methods of ge netic mapping and gene cloning used for other complex diseases will be appl ied to cancer, these must almost certainly be complemented by other methods , such as the study of somatic mutations, cancer associated phenotypes, and modifier genes for Mendelian cancers. Here, we review the strategies avail able for identifying cancer predisposition genes of low and moderate penetr ance.