Clinical definition of hereditary non-polyposis colorectal cancer: A search for the impossible?

Hereditary non-polyposis colorectal cancer is an autosomal dominant inherit ed disorder that predisposes its carriers to an almost 100% lifetime risk o f cancer, in particular colorectal and endometrial cancer. Germline mutatio ns, resulting in a deficient DNA mismatch repair system. are responsible fo r the disease. Because of the lack of specific phenotypical features, clini cal diagnosis in an individual patient is impossible and relies heavily on family history. Genetic diagnosis by mismatch detection is now possible in a substantial proportion of families. Thus there is a great need for reliab le but simple criteria that will help clinicians to recognize patients and families who can be referred for genetic diagnostics. In this article the d ifferent criteria that have been formulated and published in recent years a re reviewed and the results, in terms of the proportions of subjects satisf ying the criteria who were found to have a germline mutation, are discussed . In most studies the criteria were evaluated in only a small number of sub jects. A population-based study is currently being carried out in the north of The Netherlands that aims to include 400 patients fulfilling one of a f ew simple criteria. Mutation analysis will be performed in all patients, Th e results of this study will help in the formulation of accurate and simple criteria for use in clinical practice.