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The Mallorca group was formed by European members when InSiGHT was established 10 years ago to facilitate, coordinate and compile European research on inherited colorectal cancer syndromes and issue clinical guidelines (http://www.ncbi.nlm. nih.gov/pubmed/23408351). It is this year transformed into The European Hereditary Tumour Group (EHTG), open for world-wide membership (contact: Gabriela.Moeslein@helios-kliniken.de). The European MMR cDNA Working Group is focusing on in-vitro testing for determining pathogenicity of MMR gene variants (holinskifeder@ mgz-muenchen.de).
The Prospective Lynch Syndrome Database ( moller.pal@gmail. com) established 2013, is open for all to join. The goal is to migrate knowledge on Lynch Syndrome (LS) from educated guesses based on retrospective series invalidated by selection biases, to prospectively obtained empirical knowledge and revise clinical guidelines accordingly. Classification of mutations is made in collaboration with InSiGHT’s (http://insight-group.org/) Variant Interpretation Committee (VIC, contact: Maurizio.Genuardi@unicatt.it) and the LOVD database (http://chromium.lovd.nl/LOVD2/colon_cancer/), where all genetic variants are classified (http://www.ncbi.nlm.nih. gov/pubmed/24362816 ) and which is now recognized by HVP as the reference database for MMR mutations. Large numbers are needed to arrive at reliable results. The database currently includes ~3,200 LS patients prospectively observed for ~25,000 years. Results currently published (http://www.ncbi.nlm.nih.gov/pubmed/26657901) or in preparation include: Colonoscopy with removal of adenomas does not prevent colorectal cancer as assumed, but survival when cancer occurred was excellent. A 3 year interval was neither associated with lower incidence of colorectal cancer nor worse survival than shorter intervals between colonoscopies. Endometrial cancer had the highest lifetime incidence and had excellent survival. Ovarian cancer was seen early in life and most were cured. We now have a growing and aging cohort of LS patients who have survived both their first and subsequent cancers. Among these, path_MLH1 carriers have a high incidence of upper gastrointestinal cancers with serious prognosis, while path_MSH2 carriers have high incidence of urinary tract cancers with good prognosis but some get brain or gastric tumours with serious prognoses. Path_MSH6 carriers had as high incidence of endometrial cancer, but relatively low lifetime risk for colorectal cancer. Path_PMS2 carriers had, besides a few cases with endometrial and prostate cancers, no incidence of LS associated cancers. We have established the web-site http://lscarisk.org where risk for cancer according to age, genotype and gender may be calculated for any LS patient’s actual age which may be instrumental for genetic counselling.