Invited Lecture(JSGE)
Fri. November 6th   14:00 - 14:30   Room 7: Portopia Hotel South Wing Ohwada C
Invited Lecture2
 Hereditary colorectal tumors
Evelien Dekker
Department of Gastroenterology & Hepatology, Amsterdam University Medical Centers
Many adults will have a relative, friend, neighbor or colleague affected by colorectal cancer (CRC). This is not surprising, as CRC is among the most commonly diagnosed types of cancer worldwide and in a Western population the lifetime risk of developing CRC is approximately 5%. Of all CRC cases, an estimated 15-20% is related to familial or hereditary factors. The majority of cases with multiple first- and second-degree family members with CRC are classified as Familial CRC (FCC), in whom no underlying genetic cause has been identified so far. Approximately 3-6% of all CRCs have a well-defined inherited genetic predisposition. These hereditary CRC syndromes can be classified as either diseases that are characterized by the presence of multiple colorectal polyps (polyposis) or only several polyps (non-polyposis), of which Lynch-syndrome is the most prevalent. Because of its phenotype, polyposis syndromes are usually diagnosed, and the histological subtype of polyps generally leads to the appropriate diagnosis. The diagnosis of Lynch-syndrome is often missed, although diagnosis is important for appropriate surveillance programs. Strategies of universal or more selective molecular testing of CRCs (IHC or MSI) or systematic questionnaires on family history have the potential for better identification of this syndrome.
Two new germline mutations for Lynch syndrome have been identified in the past decade: PMS-2 and EPCAM. Due to the accelerated adenoma-carcinoma pathway in Lynch-syndrome, quality indicators for colonoscopy as well as appropriate intervals and adherence to these surveillance intervals are of utmost importance. Patients with MSH-6 and PMS-2 have appeared at a later and lower risk for CRC than patients with other Lynch-mutations, and starting age for surveillance might be extended. For polyposis syndrome, it is the number of polyps and balanced decision-making in endoscopic vs surgical interventions that determines quality of care, which should be delivered in expert centers.
Serrated polyposis syndrome does not seem to be a monogenetic syndrome. However, its prevalence is higher than that of other polyposis syndromes. In the past more CRCs occurring in patients in this syndrome were interpreted as having arisen by an accelerated serrated pathway to CRC, but more probably are caused by an inadequate detection of serrated polyps and/or recognition of the disease.
Chemoprevention would be ideal for those at an increased risk for CRC, however, first evidence for effective medications have become available only very recently, and more research should be performed.
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