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Family History, Surgery, and APC Mutation Are Risk Factors for Desmoid Tumors in Familial Adenomatous Polyposis: An International Cohort Study

Nieuwenhuis, Marry H. M.D., M.Sc.; Lefevre, Jérémie H. M.D.; Bülow, Steffen M.D., Ph.D.; Järvinen, Heikki M.D., Ph.D.; Bertario, Lucio M.D., Ph.D.; Kernéis, Solen M.D.; Parc, Yann M.D., Ph.D.; Vasen, Hans F. A. M.D., Ph.D.

doi: 10.1097/DCR.0b013e318227e4e8
Original Contribution

BACKGROUND: Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice.

OBJECTIVES: Our aim was to assess several risk factors for desmoid tumor development in an international cohort of patients with familial adenomatous polyposis and to evaluate the clinical relevance of risk factors.

DESIGN: This was a retrospective cohort study.

SETTING AND PATIENTS: Polyposis registries in The Netherlands, France, Denmark, Finland, and Italy provided information on familial adenomatous polyposis patients with desmoid tumors.

MAIN OUTCOME MEASURES: We used univariate and multivariable analyses of data from registries in The Netherlands, France, Denmark, and Finland to test whether gender, APC mutation site, previous colorectal surgery, colorectal cancer, and family history for desmoid tumors contribute to risk of developing desmoid tumors at any location, or specifically at an intra-abdominal location. The effect of family history was tested with a generalized linear mixed model.

RESULTS: Of 2260 patients with familial adenomatous polyposis from 912 families in The Netherlands, France, Denmark, and Finland, 220 patients (10%) had desmoid tumors (101 men). In 387 patients with desmoid tumors (including 167 patients from the Italian registry), the median age at diagnosis of the first desmoid tumor was 31 years (range, 4 months–74 years). Desmoid locations were intra-abdominal (53%), abdominal wall (24%), extremities (9%), and unknown sites or combinations of sites (14%). Multivariable analysis of risk factors for desmoids at any location showed surgery (OR, 2.58; P = .0004), an APC mutation 3′ of codon 1444 (OR, 3.0; P < .0001), and a positive family history (P < .0001) to be independently associated with desmoid development. When only intra-abdominal location was analyzed, APC mutation site was not associated with desmoid development.

LIMITATIONS: Selection bias may have occurred.

CONCLUSIONS: A positive family history for desmoid tumors, abdominal surgery, and APC mutation site are significant risk factors for development of desmoid tumors. The results may have implications for determining the optimal management of FAP patients and guide future studies.

1 The Netherlands Foundation for the Detection of Hereditary Tumors, Leiden, The Netherlands

2 Department of Digestive Surgery, Hospital Saint-Antoine, AP-HP, University Pierre et Marie Curie Paris VI, Paris, France

3 The Danish Polyposis Register, Department of Surgery, Hvidovre University Hospital, Hvidovre, Denmark

4 Department of Surgery, University of Helsinki, Helsinki, Finland

5 Department of Predictive and Preventive Medicine, National Cancer Institute, Milan, Italy

6 Cochin-Pasteur Vaccinology Center (CIC BT505), Université Paris Descartes, INSERM, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France

7 Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands

Financial Disclosure: None reported.

Presented at the meeting of the International Society for GI Hereditary Tumours, San Antonio, TX, March 30 to April 2, 2011.

Correspondence: Marry H. Nieuwenhuis, M.D., M.Sc., The Netherlands Foundation for the Detection of Hereditary Tumors, Rijnsburgerweg 10, Poortgebouw Zuid, 2333 AA Leiden, The Netherlands. E-mail:

© 2011 The American Society of Colon and Rectal Surgeons