Mutation detection in the mismatch repair genes is best focused on affected individuals who are part of a family that satisfies the modified Amsterdam criteria. These were designed to identify useful research families, but are also valuable in targeting diagnostic resources. Suitable individuals belong to families in which there have been at least three cancers in people where one is a first degree relative of the other two. For example, a woman, her son and her brother. Provided they have colorectal cancer and/or endometrial or gastric cancer and one had onset before 50 years of age, there is a >90% probability that a mutation in MSH2 or MLH1 will be detected. Almost all tumours resulting from defects in these mismatch repair genes display a characteristic instability of the DNA microsatellite markers used in traditional genetic linkage studies. Immunohistochemistry for the protein product of MSH2 is also valuable as its absence is a strong indication of mutation in the MSH2 gene. This technique is less effective for MLH1 because a large proportion of sporadic colorectal cancers lose expression of this protein due to a reversible suppression of gene expression.

Mutation detection in the BRCA genes is best focused on families where there have been at least four affected individuals in multiple generations. Families that feature breast and ovarian cancers, bilateral cancers in young women and male breast cancer are all worthy of diagnostic testing. The primary problem is the slow development of these molecular diagnostic services. Urgent investment in laboratory facilities and staff training is needed to prepare for the expansion of diagnostic need. It is estimated that overall at least 5% of the common cancers other than lung cancer have a single gene defect underlying them that would be amenable to predictive testing and more effective prevention and therapy. In pure health economic terms the benefits are obvious of catching early a solid tumour allowing cure rather than prolonged palliation of cases diagnosed later. Unfortunately, the financial benefits of cure affect different aspects of health care to the services called upon to deliver diagnostic genetic services. There is a willingness of European genetics centres to integrate their work. This is threatened by the need to compete in a more commercial setting and by the patenting of genes such as BRCA1. Gene patenting can hamper the rapid development and dispersal of diagnostic tests and is likely to restrict fulfilment of the potential of genetic testing in cancer prevention.