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Prevalence of Adenomas and Hyperplastic Polyps in Mismatch Repair Mutation Carriers Among CAPP2 Participants: Report by the Colorectal Adenoma/Carcinoma Prevention Programme 2

Annelie Liljegren, Gail Barker, Faye Elliott, Lucio Bertario, Marie Luise Bisgaard, Diana Eccles, Gareth Evans, Finlay Macrae, Eamonn Maher, Annika Lindblom, Samuel Rotstein, Bo Nilsson, Jukka-Pekka Mecklin, Gabriela Möslein, Jeremy Jass, Riccardo Fodde, John Mathers, John Burn, D. Timothy Bishop

From the Department of Clinical Genetics, Centre for Molecular Medicine, and Institution of Oncology and Pathology, Unit of Cancer Epidemiology, Radiumhemmet, Karolinska University Hospital; Oncology Unit of Radiumhemmet at Danderyds Hospital, Stockholm, Sweden; Institute of Human Genetics Annex, Bioscience Centre; Human Nutrition Research Centre, School of Clinical Medical Sciences University of Newcastle, Newcastle upon Tyne; Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Genetics Building, St James's University Hospital, Leeds; Clinical Genetics Unit, Southampton; Department of Medical Genetics, Manchester; University of Birmingham, Head Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, Birmingham, United Kingdom; Instituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy; Danish Hereditary Nonpolyposis Colorectal Cancer Registry, Gastroenheden 435, Hvidovre Hospital and Medical, Genetics Clinic, Panum Institute 24.4, Copenhagen University, Coppenhagen, Denmark; Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Victoria, Australia; Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland; Chirurgische Klinik und Poliklinik, Düsseldorf, Germany; Department of Pathology, McGill University, Montreal, Quebec, Canada; Department of Human and Clinical Genetics, Leiden; and Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, the Netherlands

Corresponding author: Annelie Liljegren, MD, PhD, The Oncology Unit of Radiumhemmet at Karolinska University Hospital, Stockholm, Sweden 171 76; e-mail: annelieliljegren{at}yahoo.com

Purpose To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously in smaller studies, and the results have been found to be variable.

Patients and Methods Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before the chemoprevention study were the focus of this study. The number, histology, size, and location of polyps found at the participants' first ever colonoscopy were analyzed in a cross-sectional study.

Results Seventy-four patients (10.6%) were found to have at least one adenoma at first colonoscopy, whereas 37 (5.3%) had at least one hyperplastic polyp. The frequency of an adenoma at first colonoscopy increased from 5.0% (95% CI, 2.8% to 8.3%) in patients younger than 35 years old to 18.9% (95% CI, 9.4% to 32.0%) in patients age at least 55 years (P = .0001 for trend). No such trend was observed for hyperplastic polyps. No sex differences were found for either type of polyp. A marginal association was found between the co-occurrence of adenomas and hyperplastic polyps. Adenomas tended to be more proximally distributed through the colon, whereas hyperplastic polyps tended to be located in the distal colon.

Conclusion Adenoma prevalence increases with age among MMR mutation carriers, whereas hyperplastic polyp prevalence is consistent. No sex differences were observed for either type of lesion.

Supported by European Union European Commission Directorate General XII Science, Research and Development–Joint Research Centre Life Sciences Technologies Medical Research, Brussels, Belgium; Cancer Research UK, London, United Kingdom; Medical Research Council, London, United Kingdom; Bayer AG GB Consumer Care Medizin Gebäude, Leverkusen, Germany; National Starch and Chemical Company Natural Polymer Research, Bridgewater, NJ; Cancer Council Victoria, Carlton, Victoria, Australia; Swiss Institute for Applied Cancer Research, Coordinating Centre, Bern, Switzerland; Newcastle upon Tyne Hospitals, National Health Services Trust Special Trustees, Freeman Hospital, Newcastle upon Tyne, United Kingdom; Nilsson-Ehle Foundation in Sweden; and Finnish Cancer Foundation and Sigrid Juselius Foundation in Finland.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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