The past two decades have seen rapid progress towards the mapping and identification of genes involved in inherited predisposition to cancer. Before 1987, no genes conferring a high inherited risk of cancer had been identified or even localized; at that time the only genetic loci known to be involved in cancer predisposition were the HLA system, where certain HLA haplotypes were known to predispose to Hodgkin’s disease1 and to nasopharyngeal cancer,2 and the ABO blood group, where stomach cancer had been shown to be slightly more common in individuals with group A.3 All of these associations are, however, quite weak. This situation was transformed in the 1980s by the development of techniques for typing DNA polymorphisms, which could be used for linkage analysis.4 In 1987, the loci for familial adenomatous polyposis5 and multiple endocrine neoplasia6,7 were first localized, and, since then, genes for all the major ‘inherited cancer syndomes’ (i.e. those rare syndromes where evidence for Mendelian inheritance was apparent from clinical studies) have been identified (see Chapter 1).