Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet

Department of Gastroenterology, Leiden University Medical Centre, Leiden, The Netherlands.
Journal of Medical Genetics (Impact Factor: 6.34). 07/2007; 44(6):353-62. DOI: 10.1136/jmg.2007.048991
Source: PubMed


Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.

Download full-text


Available from: Gabriel Capellá, Sep 30, 2015
91 Reads
  • Source
    • "Screening guidelines recommend colonoscopy screening for those older than 50 years [4]. All participating respondents therefore were 50 years or older and a US resident. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The value of the information that genetic testing services provide can be questioned for insurance-based health systems. The results of genetic tests oftentimes may not lead to well-defined clinical interventions; however, Lynch syndrome, a genetic mutation for which carriers are at an increased risk for colorectal cancer, can be identified through genetic testing, and meaningful health interventions are available via increased colonoscopic surveillance. Valuations of test information for such conditions ought to account for the full impact of interventions and contingent outcomes. To conduct a discrete-choice experiment to elicit individuals' preferences for genetic test information. A Web-enabled discrete-choice experiment survey was administered to a representative sample of US residents aged 50 years and older. In addition to specifying expenditures on colonoscopies, respondents were asked to make a series of nine selections between two hypothetical genetic tests or a no-test option under the premise that a relative had Lynch syndrome. The hypothetical genetic tests were defined by the probability of developing colorectal cancer, the probability of a false-negative test result, privacy of the result, and out-of-pocket cost. A model specification identifying necessary interactions was derived from assumptions of risk behavior and the decision context and was estimated using random-parameters logit. A total of 650 respondents were contacted, and 385 completed the survey. The monetary equivalent of test information was approximately $1800. Expenditures on colonoscopies to reduce mortality risks affected valuations. Respondents with lower income or who reported being employed significantly valued genetic tests more. Genetic testing may confer benefits through the impact of subsequent interventions on private individuals. Copyright © 2014. Published by Elsevier Inc.
    Value in Health 12/2014; 17(8):838-45. DOI:10.1016/j.jval.2014.09.001 · 3.28 Impact Factor
  • Source
    • "Surveillance with upper endoscopy is offered to all Lynch syndrome patients every 2 years, starting from the age of 30–35 years. Annual renal ultrasound, urinalysis and urine cytology can be considered in families with a history of urinary tract tumors [58]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolu¬tion that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.
    Journal of medicine and life 03/2014; 7(1):17-26.
  • Source
    • "The syndrome is clinically classified according to the Amsterdam criteria, which require at least three HNPCC-associated cancers, two affected first-degree relatives and at least one individual diagnosed before age 50 [3], [4]. Between one-third and half of the families that fulfill the Amsterdam criteria carry germline mismatch repair (MMR) gene mutations in MLH1, MSH2, MSH6 or PMS2 and are referred to as having Lynch syndrome [5]–[7]. The remaining families with a yet unidentified genetic background show a predominance of colorectal cancer, frequent synchronous and metachronous adenomatous polyps and few extracolonic tumors and are referred to as familial colorectal cancer type X (FCCTX) [8], [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects. We addressed the gene expression signatures in colorectal cancer linked to Lynch syndrome and FCCTX with the aim to identify candidate genes and to map signaling pathways relevant in hereditary colorectal carcinogenesis. The 18 k whole-genome c-DNA-mediated annealing, selection, extension, and ligation (WG-DASL) assay was applied to 123 colorectal cancers, including 39 Lynch syndrome tumors and 37 FCCTX tumors. Target genes were technically validated using real-time quantitative RT-PCR (qRT-PCR) and the expression signature was validated in independent datasets. Colorectal cancers linked to Lynch syndrome and FCCTX showed distinct gene expression profiles, which by significance analysis of microarrays (SAM) differed by 2188 genes. Functional pathways involved were related to G-protein coupled receptor signaling, oxidative phosphorylation, and cell cycle function and mitosis. qRT-PCR verified altered expression of the selected genes NDUFA9, AXIN2, MYC, DNA2 and H2AFZ. Application of the 2188-gene signature to independent datasets showed strong correlation to MMR status. Distinct genetic profiles and deregulation of different canonical pathways apply to Lynch syndrome and FCCTX and key targets herein may be relevant to pursue for refined diagnostic and therapeutic strategies in hereditary colorectal cancer.
    PLoS ONE 08/2013; 8(8):e71755. DOI:10.1371/journal.pone.0071755 · 3.23 Impact Factor
Show more