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Research group/lab  |  PI A.Wagner, MD PhD

Hereditary Gastrointestinal Tumors

Our group has a long-standing interest in the diagnostics and clinical management of hereditary gastrointestinal tumors

About our research group/lab

Our research

We have successfully worked together with the Erasmus MC departments of Gastroenterology & Hepatology, Gynecology and Pathology on many research projects involving hereditary gastrointestinal cancer such as Lynch syndrome (LS), Peutz-Jeghers syndrome and familial pancreatic cancer. An example is the LIMO study, a large prospective cohort study in the Southwest Netherlands on routine tissue testing for LS. As a results of this study, routine tumor testing for LS in every colorectal cancer (CRC) patient diagnosed under the age of 70 years is now included in the Dutch guideline for hereditary CRC. Our work has been recognized by the Netherlands Federation of University Medical Centers (NFU), which established Erasmus MC as a center of expertise for LS.

Lynch syndrome

Lynch syndrome is the most common hereditary predisposition to colorectal cancer (CRC). It is caused by mutations in DNA repair (mismatch repair/MMR) genes. Carriers of a MMR mutation are at high risk of up to 70% of developing CRC or other cancers. Surveillance of Lynch syndrome carriers largely decreases their risk of developing cancer. Our research focuses on improving the diagnostics and surveillance for Lynch syndrome. An overview can be obtained from the doctoral theses from our group:

Towards improved detection and management of Lynch Syndrome

Hereditary colorectal cancer syndromes: Epidemiological studies on Peutz-Jeghers syndrome & Lynch syndrome

Diagnostic Strategies for Early Lynch Syndrome Detection: From Molecular Testing to Economic Evaluation

Lynch Syndrome Improving Diagnostics and Surveillance

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a rare predisposition to gastrointestinal polyps and cancer. Carriers also have characteristic pigmentations of the lips and saliva. We investigate the (cancer) risks associated with this syndrome and focus on improving surveillance for Peutz-Jeghers syndrome carriers. See also the doctoral theses from our group:

Peutz-Jeghers syndrome and cancer linked by LKB1

Hereditary colorectal cancer syndromes: Epidemiological studies on Peutz-Jeghers syndrome & Lynch syndrome

Our projects

Lynch-like project

This project focusses on finding the cause of cancer in patients with a Lynch-like tumor (MSI-H) without a germline mutation in one of the MMR genes.

Lynch surveillance study

This study evaluates the current surveillance in LS carriers and investigates how this surveillance can be optimized.

CATCA study

This project aims to develop a cell-free DNA (cfDNA) based blood test for the detection of colorectal adenomas and early colorectal cancer.

Key Publications

A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting. Ramsoekh D, Wagner A, Leerdam ME van, Dinjens WNM, Steyerberg EW, Halley JJ, Kuijpers EJ, Dooijes D. (2008). Gut. 2008 Nov;57(11):1539-44.

High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. 
Van Lier MG, Westerman AM, Wagner A, Looman CW, Wilson JH, de Rooij FW, Lemmens VE, Kuipers EJ, Mathus-Vliegen EM, van Leerdam ME. (2011). Gut. 2011;60(2):141-7.

Yield of routine molecular analysis in colorectal cancer patients <70 years to detect underlying Lynch syndrome.Van Lier MG, Leenen CH, Wagner A, Ramsoekh D, Dubbink HJ, van den Ouweland AM, Westenend PJ, de Graaf EJ, Wolters LM, Vrijland WW, Kuipers EJ, van Leerdam ME, Steyerberg EW, Dinjens WN; LIMO Study Group. (2012). J Pathol. 2012 Apr;226(5):764-74.

Somatic aberrations of mismatch repair genes as a cause of microsatellite-unstable cancers. Geurts-Giele WR, Leenen CH, Dubbink HJ, Meijssen IC, Post E, Sleddens HF, Kuipers EJ, Goverde A, van den Ouweland AM, van Lier MG, Steyerberg EW, van Leerdam ME, Wagner A, Dinjens WNJ. (2014). Pathol. 2014 Dec;234(4):548-59.

Cost-effectiveness of routine screening for Lynch syndrome in colorectal cancer patients up to 70 years of age.Leenen CH, Goverde A, de Bekker-Grob EW, Wagner A, van Lier MG, Spaander MC, Bruno MJ, Tops CM, van den Ouweland AM, Dubbink HJ, Kuipers EJ, Dinjens WN, van Leerdam ME, Steyerberg EW. (2016). Genet Med. 2016 Oct;18(10):966-73.

Cost-effectiveness of routine screening for Lynch syndrome in endometrial cancer patients up to 70years of age.Goverde A, Spaander MC, van Doorn HC, Dubbink HJ, van den Ouweland AM, Tops CM, Kooi SG, de Waard J, Hoedemaeker RF, Bruno MJ, Hofstra RM, de Bekker-Grob EW, Dinjens WN, Steyerberg EW, Wagner A, LIMO study group. (2016). Gynecol Oncol. 2016 Dec;143(3):453-459.

Small-bowel Surveillance in Patients With Peutz-Jeghers Syndrome: Comparing Magnetic Resonance Enteroclysis and Double Balloon Enteroscopy. Goverde A, Korsse SE, Wagner A, van Leerdam ME, Krak NC, Stoker J, van Buuren HR, Hofstra RM, Bruno MJ, Dewint P, Dekker E, Spaander MC. (2017). J Clin Gastroenterol. 2017 Apr;51(4):e27-e33.

Routine Molecular Analysis for Lynch Syndrome Among Adenomas or Colorectal Cancer Within a National Screening Program.Goverde A, Wagner A, Bruno MJ, Hofstra RMW, Doukas M, van der Weiden MM, Dubbink HJ, Dinjens WNM, Spaander MCW. (2018). Gastroenterology. 2018 Nov;155(5):1410-1415.


Collaboration within Erasmus MC

Our group has a long-standing collaboration with the Erasmus MC departments of Gastroenterology & Hepatology (V.M.C.W. Spaander and M.J. Bruno), Gynecology (H.C. van Doorn) and Pathology (W.N.M. Dinjens) of the regarding the diagnostics and clinical management of hereditary gastrointestinal tumors.

Collaboration outside of Erasmus MC

Our group collaborates with the Leiden University Medical Center (M. Nielsen) on improving risk estimations in Lynch syndrome. Also, we are actively involved in the INVUSE consortium, which is dedicated to classify variants of unknown significance in MMR genes.

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