Attenuated familial adenomatous polyposis: results from an international collaborative study

Authors

  • A. L. Knudsen,

    1. Danish Polyposis Register, Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark
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  • S. Bülow,

    1. Danish Polyposis Register, Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark
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  • I. Tomlinson,

    1. Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
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  • G. Möslein,

    1. Department of Surgery, St. Josefs-Hospital Bochum-Linden, Bochum, Germany
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  • K. Heinimann,

    1. Research Group Human Genetics, Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland
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  • I. J. Christensen,

    1. Danish Polyposis Register, Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark
    2. Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark
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  • The AFAP Study Group

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    • Stefan Aretz MD, Institute of Human Genetics, University Clinic of Bonn, Bonn, Germany; Terri Berk, Familial GI Cancer Registry, Mt. Sinai Hospital, Toronto, Canada; Lucio Bertario MD, Department of Surgery, National Cancer Institute, Milan, Italy; Marie Luise Bisgaard MD, Danish Polyposis Register, Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark; Steve Gallinger, Familial GI Cancer Registry, Mt. Sinai Hospital, Toronto, Canada, Canada; Judith Karner-Hanusch MD, The Austrian Polyposis Register, Vienna, Austria; Finlay Macrae MD, Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Victoria, Australia; Kay Neale, The Polyposis Registry, St. Mark’s Hospital, Harrow, United Kingdom; Maurizio Ponz de Leon MD, Department of Internal Medicine, University of Modena, Modena, Italy; Paul Rozen MD, Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel; Allan Spigelman MD, Faculty of Medicine, St Vincent’s Clinical School, University of New South Wales, Hunter Family Cancer Service, and NSW & ACT Hereditary Cancer Registers, New South Wales, Australia.


Steffen Bülow, MD, DMSc, The Danish Polyposis Register, Hvidovre University Hospital, DK-2650 Hvidovre, Copenhagen, Denmark.
E-mail : sbulow@dadlnet.dk

Abstract

Aim  The study aimed to describe genetical and clinical features of attenuated familial adenomatous polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance.

Method  A questionnaire study was carried out of polyposis registries with data on patients with presumed AFAP, defined as having ≤100 colorectal adenomas at age ≥25.

Results  One hundred and ninety-six patients were included. The median number of adenomas was 25 (0–100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty-two patients had a colectomy and an ileorectal anastomosis and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5′ end, exon 9 and 3′ end).

Conclusions  A subset of FAP patients with a milder phenotype does exist and treatment and surveillance had to be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following clinical diagnostic criteria for AFAP: a dominant mode of inheritance of colorectal adenomatosis and <100 colorectal adenomas at age 25 or older. Colonoscopy had to be preferred to sigmoidoscopy and surveillance had to be life-long. In the majority of patients, prophylactic colectomy and ileorectal anastomosis are recommended at the age of 20–25 years.

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