The genetic basis of colonic adenomatous polyposis syndromes.
Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and familial adenomatous polyposis (FAP) accounts for approximately 1% of all CRCs. Adenomatous polyposis syndromes can be divided into; familial adenomatous polyposis (FAP) - classic FAP and attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), NTHL1-associated polyposis (NAP) and polymerase proofreading-associated polyposis (PPAP). The polyposis syndromes genetics and clinical manifestation of disease varies and cases with clinical diagnosis of FAP might molecularly show a different diagnosis. This review examines different aspects of the adenomatous polyposis syndromes genetics and clinical manifestation of disease; in addition the genotype-phenotype and modifier alleles of FAP will be discussed. New technology has made it possible to diagnose some of theAPCmutation negative patients into their respective syndromes. There still remain many molecularly undiagnosed adenomatous polyposis patients indicating that there remain causative genes to be discovered and with today's technology these are expected to be identified in the near future. The knowledge about the role of modifier alleles in FAP will contribute to improved pre-symptomatic diagnosis and treatment. New novel mutations will continually be discovered in genes already associated with disease and new genes will be discovered that are associated with adenomatous polyposis. The search for modifier alleles in FAP should be made a priority.
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491 Norway.|Clinic for Medicine, Møre og Romsdal Hospital Trust, Molde, Norway.|School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW Australia.|Hunter Medical Research Institute, Newcastle, NSW Australia.|Clinic for Medicine, Library, Molde Hospital, Parkvegen 84, Molde, 6407 Norway.
Bente A
BA
Talseth-Palmer
FAP; Genetics; Genotype-phenotype; MAP; Modifier genes; NAP; PPAP