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An Overview of the Lynch Syndrome (Hereditary Non-polyposis Colorectal Cancer)

  • Hans F. A. VasenEmail author
  • J. C. H. Hardwick
Chapter
Part of the M.D. Anderson Solid Tumor Oncology Series book series (MDA, volume 5)

Abstract

Environmental factors play a dominant role in the etiology of most colo­rectal cancers. However, in about 5% of all cases, CRC is associated with a highly penetrant dominant syndrome. The most common of these is Lynch syndrome (hereditary non-polyposis colorectal cancer; HNPCC). It is characterized by the development of colorectal cancer, endometrial cancer and various other cancers and is caused by a mutation in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2. The MMR-defect leads to instability at microsatellites of tumour-DNA (microsatellite instability (MSI)) which can be found in >90% of CRC associated with Lynch syndrome. Currently, mainly clinical criteria (Bethesda criteria) are used to select patients with CRC for molecular genetic (MSI-analysis) and/or immunohistochemical analysis of the tumour and those with evidence of MSI or loss of MMR expression are offered mutation analysis. Because, there is increasing evidence that MSI/IHC is an important prognostic factor and may predict the response to chemotherapy, these tests might in future be performed on a much larger scale, if not in all CRC cases.

Identification of Lynch syndrome families is important as it allows to offer preventative measures. Many studies have shown that colonoscopic surveillance leads to a substantial reduction of the risk of CRC and also reduction of the mortality associated with CRC. Also surveillance for endometrial cancer may lead to detection of premalignant lesions and early cancers.

Knowledge on the effectiveness of surveillance for the other LS-associated cancer is limited.

The life time risk of developing one of associated cancers (stomach, ureter, renal pelvis, small bowel, the bile ducts and tumors of the brain) is relatively low (less than 15%) and may be associated with the underlying MMR defect. In the decision making on which surveillance protocol should be recommended, a reasonable approach might be to first discuss all the various cancer risks with the patient, then discuss which screenings are indicated scientifically.

In this chapter, the clinical features, diagnostic criteria and management of the syndrome will be discussed in detail.

Keywords

Overview Lynch syndrome Hereditary Non-polyposis Colorectal cancer HNPCC 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of GastroenterologyUniversity Medical CentreLeidenThe Netherlands
  2. 2.Medical OncologyLeiden University Medical CentreLeidenThe Netherlands
  3. 3.The Netherlands Foundation for the Detection of Hereditary TumoursLeiden University Medical Centre (Poortgebouw)LeidenThe Netherlands

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