Detection and prevention of Hereditary intestinal cancers

Since 1985, Professor Hans Vasen is staff member of the department of Gastroenterology and Hepatology of the LUMC as well as Medical Director of the Dutch Hereditary Cancer Registry. The research of professor Vasen focuses mainly on three hereditary cancer syndromes and a few other rare hereditary cancer syndromes: 

  1. Lynch syndrome; 
  2. familial adenomatous polyposis; 
  3. hereditary pancreatic cancer and 
  4. other rare hereditary cancer syndromes including CMMRD, PTEN-syndrome and SMAD4-polyposis 

Part of the research is conducted in collaboration with the Dutch Hereditary Cancer Registry (Stichting Opsporing Erfelijke Tumoren (StOET)). The aims and results of the Registry are described below followed by a short summary of studies performed on  the various hereditary cancer syndromes.

Hereditary Cancer Registry

In 1985, Vasen and others established a Registry of families with hereditary cancer including Lynch syndrome and Polyposis-syndromes. The aims of this registry are: 

(a) to promote the identification of families with hereditary cancer, 
(b) to encourage the participation in surveillance programs of individuals at high risk, 
(c) to ensure the continuity of lifelong surveillance examinations, and 
(d) to promote research, in particular the development of safe surveillance protocols. 

Since its founding, the registry has identified over 10,000 high-risk individuals with a diverse array of hereditary cancer syndromes, in particular, Lynch syndrome, familial adenomatous polyposis (FAP/MUTYH), hereditary melanoma, hereditary breast cancer and hereditary prostate cancer.  All were encouraged to participate in prevention programmes. 

Lynch syndrome

We have published a number of studies that evaluated the outcome of colonoscopic surveillance for colorectal cancer (CRC) in Lynch syndrome. In 2006, evaluation of the effect of registration and surveillance on the mortality rate associated with colorectal cancer (CRC) showed that the policy led to a substantial decrease in the mortality rate associated with CRC. Following discovery of MMR gene defects, the first predictive model that could select families for genetic testing was published by the Leiden group. In addition, over the years the registry has produced many cancer risk studies that have helped to develop appropriate surveillance protocols. In 2007 and 2013 guidelines were published for the management of this disorder. The current research includes an assessment of the cancer risk in Lynch syndrome families, the influence of nutrition on the development of adenomas and an evaluation of the best surveillance interval in three European countries (Finland, Germany and the Netherlands). In 2017, we started an intervention trial comparing the effect of mesalazine versus placebo on the development of adenomas in LS patients (as part of a European project (MESACAP Transcan)). We also contributed to the recently established prospective Lynch syndrome database (PLDS) (Møller et al) that recently reported new cancer risk estimates.

Familial adenomatous polyposis (FAP)

Shortly after establishment of the registry, the research addressed the application of genetic tests in FAP and the association between genotype and phenotype. Our research group was one of the first that suggested to use the outcome of genetic tests as guide for the surgical management of FAP. In the next years we evaluated the best surgical treatment for FAP: ileorectal anastomosis or proctocolectomy. To this aim we evaluated the risk of developing cancer in the pouch after total proctocolectomy and compared the functional outcome and quality of life between an ileorectal anastomosis and proctocolectomy with construction of an Ileo-anal pouch anastomis. In 2008, we published European guidelines for the management of FAP. At the same time we evaluated psychosocial issues and compliance in FAP. In the last decade we studied extracolonic manifestations of FAP including desmoid tumors, duodenal polyposis and non-GI-cancer and the influence of SNP's on the development of polyposis.

Hereditary Pancreatic Cancer

The Leiden University Medical Centre is an expertise centre for the management of families with hereditary melanoma (FAMMM)(Prof. W. Bergman, Department of Dermatology). This syndrome is caused by a CDKN2A-P16-Leiden-mutation, a founder mutation, which is very common in the area of the LUMC (Katwijk, Roelofarendsveen). Carriers of a CDKN2A/p16-Leiden mutation are not only at risk of development of melanoma, but also pancreatic cancer, cancer of the larynx, pharynx and lungs.

In 2000, we started an MRI-based surveillance program at the Department of Gastroenterology & Hepatology of the LUMC for the early detection of pancreatic cancer in carriers of  this mutation. In 2015, we established collaboration with other expert centres in Europe (Madrid, Spain & Marburg, Germany). In 2016, the first results of this collaboration on hereditary pancreatic cancer were published in the Journal of Clinical Oncology and Gut. Our studies showed that the surveillance program substantially improved the prognosis of patients that develop pancreatic cancer. The current research focuses on further improvement of the surveillance program, the role of tumor markers and analysis of risk factors for the development of pancreatic cancer.

PTEN-hamartoma syndrome and constitutional mismatch repair deficiency (CMMRD)

The last 5-10 years, we are very much interested in the (multidisciplenary) management of families with highly complex disorders including families with Cowden syndrome (PTEN), and patients with constitutional mismatch repair deficiency (CMMRD).  These syndromes have in common that the patients are at high risk of developing multiple cancers including brain tumors (PTEN and CMMRD), cancer of colorectum (PTEN and CMMRD), small bowel (CMMRD), thyroid and breast (PTEN) and other cancers. All these patients need special care and psychological support. Recently, we have developed National (PTEN) and European (CMMRD) guidelines for surveillance. In order to get sufficient numbers of families we have set up European collaboration for CMMRD (Care4CMMRD).

10 Selected publications out of 433 publication (see also pubmed)

  1. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453-6.
  2. de Jong AE, Hendriks YM, Kleibeuker JH et al. Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology. 2006;130(3):665-71.
  3. Wijnen JT, Vasen HF, Khan PM et al. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med. 1998;339(8):511-8.
  4. Tops CM, Wijnen JT, Griffioen G et al. Presymptomatic diagnosis of familial adenomatous polyposis by bridging DNA markers. Lancet. 1989;2(8676):1361-3
  5. Vasen HF, van der Luijt RB, Slors J et al. Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis.Lancet. 1996;348(9025):433-5.
  6. van Duijvendijk P, Slors JF, Taat CW et al. Functional outcome after colectomy and ileorectal anastomosis compared with proctocolectomy and ileal pouch-anal anastomosis in familial adenomatous polyposis. Ann Surg. 1999;230(5):648-54.
  7. Vasen HF, Möslein G, Alonso A et al. Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut. 2008;57(5):704-13.
  8. Vasen HF, Blanco I, Aktan-Collan K et al. Revised guidelines for the clinical management of Lynch syndrome : recommendations of a group of European experts. Gut 2013; 62:812
  9. Douma KF, Aaronson NK, Vasen HF, Gerritsma MA, Gundy CM, Janssen EP, Vriends AH, Cats A, Verhoef S, Bleiker EM. Psychological distress and use of psychosocial support in familial adenomatous polyposis. Psychooncology. 2010;19(3):289-98.
  10. Vasen HF, Ibrahim I, Ponce I, et al. Benefit of surveillance for pancreatic cancer in high risk individuals: Outcome of longterm prospective follow-up studies from three European expert centres. Journal of Clinical Oncology 2016;34:2010