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Original article
Evidence for accelerated colorectal adenoma–carcinoma progression in MUTYH-associated polyposis?
  1. M H Nieuwenhuis1,
  2. S Vogt2,
  3. N Jones3,
  4. M Nielsen4,
  5. F J Hes4,
  6. J R Sampson3,
  7. S Aretz2,
  8. H F A Vasen1,5,6
  1. 1The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, the Netherlands
  2. 2Institute of Human Genetics, University of Bonn, Germany
  3. 3Institute of Medical Genetics, School of Medicine, Cardiff University, UK
  4. 4Center of Human and Clinical Genetics, Leiden University Medical Center, the Netherlands
  5. 5Department of Gastroenterology, Leiden University Medical Center, the Netherlands
  6. 6Department of Hepatology, Leiden University Medical Center, the Netherlands
  1. Correspondence to H F A Vasen, The Netherlands Foundation for the Detection of Hereditary Tumours, Rijnsburgerweg 10, Poortgebouw Zuid, Leiden 2333 AA, the Netherlands; hfavasen{at}


Background and aim MUTYH-associated polyposis (MAP) is an autosomal recessive inherited disorder characterised by the development of polyposis in the upper and lower gastrointestinal tract and a high risk of colorectal cancer (CRC). We evaluated the natural history of the disease and the outcome of colorectal surveillance and management.

Methods A large Western European dataset of biallelic MUTYH mutation carriers comprising 254 patients was used. Detailed information was collected on polyp and cancer development in the colorectum, and the outcome of surveillance and surgery. Survival methods were used to calculate the risk of CRC development.

Results The mean follow-up was 9.8 years. Colorectal polyposis was diagnosed at a mean age of 44.8 years (range: 12–77 years). Most patients had <100 colorectal adenomas at diagnosis. CRC was diagnosed in 147 (58%) of the 254 patients (mean age at diagnosis: 48.5, range: 21–77 years). The cumulative lifetime risk of CRC was 63% at age 60 years. There was no correlation between the number of adenomas and the presence of CRC. The cumulative risk of CRC in patients presenting with polyps was 9% after 5 years of follow-up. Patients presenting with CRC had 11% risk of developing a metachronous CRC at 5 years after surgery. Thirty-seven per cent of patients with MAP with CRC who underwent partial colonic resection needed secondary surgery shortly afterwards.

Conclusions The high risk of developing CRC under surveillance in patients with MAP may suggest an accelerated carcinogenesis. Surveillance of these patients should therefore include colonoscopy at short intervals, for example, at 1–2-year intervals starting from the age of 18 to 20 years. If surgery for CRC is warranted, a (sub)total colectomy is recommended.

  • MUTYH-associated polyposis
  • MAP
  • colorectal cancer
  • polyposis

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  • Funding Wales Gene Park, Cardiff, United Kingdom Dutch Digestive Disease Foundation (grant no. MWO 0355), Nieuwegein, the Netherlands.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of The Multi-Centre Research Ethics Committee for Wales, ref. 06/MRE09/19; medical faculty of the University of Bonn Ethics Review Board, no. 063/04 and Leiden University Medical Centre Ethics Review Board, no P01.019.

  • Provenance and peer review Not commissioned; externally peer reviewed.