Hereditary Gastrointestinal Tumors

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 (LS) is the most common hereditary predisposition to colorectal cancer (CRC). It is caused by germline pathogenic variants (PV) in DNA mismatch repair (MMR) genes. Carriers of an MMR PV are at high lifetime risk of up to about 55% of developing CRC, compared to about 5% in the general population. Also, there is a risk of other cancers especially endometrial cancer in female PV carriers. Surveillance of Lynch syndrome carriers largely decreases their risk of developing cancer. Our research focuses on improving the detection of LS and prevention of LS associated tumors. An overview can be obtained from the doctoral theses from our group for which you find the links below.

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is a rare predisposition to hamartomatous gastrointestinal polyps and cancer. It is caused by PV in the STK11-gene and inherits in an autosomal dominant way. Carriers also have characteristic pigmentations of the lips and saliva. We focus on determining 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 via the links below.

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

Peutz-Jeghers syndrome and cancer linked by LKB1

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

From Molecular Testing to Economic Evaluation

Lynch Syndrome Improving Diagnostics and Surveillance 

Detection, management and prevention of Lynch syndrome associated tumors

Lynch surveillance study

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

SMART study

This study tries to develop a ctDNA based blood test to improve early detection of colorectal cancer in LS carriers, and maybe also other cancers for which no good surveillance is available at the moment.

PREDI-LYNCH

This is a European collaboration in order to validated non-invasive liquid biopsy tests for cancer PREDIction in LYNCH syndrome.

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.

The management of Peutz-Jeghers syndrome: European Hereditary Tumour Group (EHTG) Wagner A, Aretz S, Auranen A, Bruno M. J., M. Cavestro G, Crosbie E.J., Goverde A, Jelsig A,M., Latchford A, van Leerdam M.E., Lepisto A, Puzzono M, Winship I, Zuber V, Möslein G. Guideline. J Clin Med 2021 Jan 27;10(3):473

Unexplained mismatch repair deficiency: Case closed. Eikenboom EL, Moen S, van Leeuwen L, Geurts-Giele WRR, Tops CMJ, van Ham TJ, Dinjens WNM, Dubbink HJ, Spaander MCW, Wagner A. HGG Adv. 2022 Dec 14;4(1):100167

Metachronous Colorectal Cancer Risk according to Lynch syndrome pathogenic variant after extensive vs partial colectomy in the Netherlands: a retrospective cohort study. Lancet Gastroenterology 2023. Eikenboom EL, Moen S, Leerdam ME. van, Papageorgiou G, Doukas M, Tanis PJ, Dekker E, Wagner A, Spaander MCW. Dec;8(12):1106-1117

Outcomes of endometrial cancer prevention strategies in patients with Lynch syndrome: a nationwide cohort study in the Netherlands. Eikenboom EL, Van Leeuwen L, Groenendijk F, Woolderink JM, Van Altena AM, Van Leerdam ME,  Spaander MCW, Van Doorn HC and Wagner A. EClinicalMedicine. 2024 Dec 21:79:103006. PMID: 39816931

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 (H.J.Dubbink and F. Groenendijk) and other collaborators within the Center for Familial and Hereditary Tumors of the Erasmus MC Cancer Institute regarding the detection and prevention of hereditary gastrointestinal tumors.

Collaboration outside of Erasmus MC

There is a good collaboration with the foundation for the detection of hereditary tumors (StOET). We are actively involved in the INVUSE consortium, which is dedicated to classify variants of unknown significance in MMR genes. We are member of the ERN GENTURIS