Clinical—Alimentary TractExpanded Extracolonic Tumor Spectrum in MUTYH-Associated Polyposis
Section snippets
Patients and Sample Collection
Index patients had an adenomatous polyposis and were referred to 1 of 3 participating centers (Institute of Human Genetics, Bonn, Germany; Institute of Medical Genetics, Cardiff, UK; Centre for Human and Clinical Genetics, Leiden, The Netherlands) for mutation analysis of the MUTYH gene that was performed as described previously.5, 12, 19 Index cases with biallelic MUTYH mutations (MAP patients) and their affected relatives were contacted and offered participation in the study. In addition, all
Results
Three-hundred and forty-six MAP patients with biallelic MUTYH mutations were approached and written consent was given by 293. Sufficient medical information could be obtained from 276 MAP patients (181 apparently unrelated index cases and 95 affected relatives) for inclusion in the study. The mutation spectrum and some phenotypic features of a subset of these patients have been described previously.3, 5, 12, 20 The characteristics of the patient groups from each participating country are
Discussion
Since its first description as an adenomatous colorectal polyposis in 2002, a number of extracolonic manifestations of MAP have been described.2, 5, 6, 12, 16, 17, 18 However, many lesions have been reported sporadically and could suggest coincidence with limited clinical relevance. In this collaborative study involving 3 European centers, we undertook a comprehensive retrospective analysis of 276 MAP patients, the largest cohort to date, and assessed the incidence of both malignant and benign
Conclusions
We evaluated the spectrum and incidence of gastroduodenal and extraintestinal tumors in the largest cohort of MAP patients examined so far. Although no predominant cancer was apparent, the overall incidence of extraintestinal malignancies was increased. The tumor spectrum associated with MAP is wider than previously recognized and there are phenotypic overlaps with Lynch syndrome. No genotype-phenotype correlation was found for extracolonic lesions. The presence of osteomas or desmoids in a
Acknowledgments
We thank the patients and families who agreed to participate in the study and A Donaldson, D Eccles, E Edwards, DG Evans, F Lalloo, E Maher, and S Palmer-Smith and all the Dutch and German doctors that assisted with recruitment. The authors also thank the Mallorca group of European experts on hereditary gastrointestinal tumors for its helpful discussions.
Databases: OMIM 608456 (MAP); Human Gene Mutation Database (HGMD):http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/9315115.html; MUTYH Leiden Open
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Conflicts of interest The authors disclose no conflicts.
Funding The study was supported by the German Cancer Aid (Deutsche Krebshilfe e.V. Bonn, grant no. 106244), part funded by Cancer Research Wales, the Wales Office of Research and Development through the Wales Gene Park, and the Dutch Digestive Diseases Foundation (grant no. MWO 0355).