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Introduction
Lynch syndrome (LS) (previously referred to as hereditary non-polyposis colorectal cancer; HNPCC) is an autosomal dominant condition caused by a defect in one of the mismatch repair (MMR) genes. 1 The syndrome is characterised by the development of colorectal cancer (CRC), endometrial cancer (EC) and various other cancers frequently diagnosed at an early age. LS is probably the most common hereditary CRC syndrome accounting for approximately 1-3% of all CRC. It has been estimated that in Europe approximately one million individuals are carriers of an MMR defect. 2
In 2007, a group of European experts (the Mallorca group) published guidelines for the clinical management of LS. 3 Since then substantial new information has become available necessitating an update of the guidelines. We used the same approach as for the development of the previous guidelines. In 2011 and 2012 workshops were organised in Palma de Mallorca. A total of 35 specialists from 13 countries participated in the meeting. The group consisted of surgeons, clinical geneticists, molecular geneticists, pathologists, oncologists, epidemiologists and gastroenterologists. If a particular speciality was not represented specialists outside the group were consulted.
The first step was to formulate important clinical questions. Then a systematic literature search was performed using the Pubmed database and manual searches of relevant articles. During the workshops the outcome of the literature search was discussed in detail. Table 1 shows the criteria that were used for evaluation of studies, for the categorisation of evidence that they represented and for the strength of the recommendations that were made.
Table 1
| Category of evidence | Grading of recommendations | |
| Meta-analysis of randomised controlled trials | Ia | A |
| Randomised controlled trial | Ib | A |
| Well-designed controlled study without randomisation | IIa | B |
| Well-designed quasi-experimental study | IIb | B |
| Non-experimental descriptive study | III | B |
| Expert opinion | IV | C |
Short update on LS
LS was first described by Aldred Warthin in 1913. 4 In 1966, Henry Lynch reported two large families with hereditary CRC from the midwest. 5 Since then, many hundreds of families with the same pattern of cancer occurrence have been identified throughout the world. In the early 1990s the underlying gene defect was discovered, that is, a mutation in one of the MMR genes MLH1, MSH2, MSH6 or PMS2. Recently, two groups reported...