Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome: Appendix 1

Abstract

Within groups of patients with colorectal cancer who report a family history of cancer, it is possible to identify cases associated with defined genetic susceptibility syndromes. These syndromes account for a small, but appreciable, proportion of all cases of colorectal cancer and are characterised by very high absolute cancer risk. There is usually evidence of germline transmission of a dominant gene associated with bowel cancer susceptibility, but there is frequently an excess of other cancer types in the family. Genes responsible for these syndromes have been identified, although some families have been identified where linkage to all known genes has been formally excluded. Hence, it is likely that there are other dominant genes that have yet to be identified. This implies that at risk people can be identified in two ways; empirically on the basis of family history or clinical and pathological criteria, or by molecular analysis of the respective gene. Although there are other rare syndromes associated with colorectal cancer risk, in the interests of clarity this guideline is restricted to discussion of hereditary non-polyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), juvenile polyposis (JP), and Peutz-Jeghers syndrome (PJS). The syndromes are defined and summarised in Online Inheritance in Man (OMIM), for which the OMIM ID numbers are given for each syndrome and the respective URL in the appendix. The molecular aetiology for each of these syndromes is listed in appendix 1. It has been shown that some people who carry pathogenic mutations of one of the causative genes do not have a strong family history of colorectal cancer. Hence, it is essential to define people at risk either by family history that fulfils inclusion criteria or those carrying a mutation in the respective gene. Screening and surveillance issues for these families must be considered separately from that recommended …