6533b860fe1ef96bd12c3968
RESEARCH PRODUCT
Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium
Pål MøllerToni SeppäläJames G. DowtySaskia HauptMev Dominguez-valentinLone SundeInge BernsteinChristoph EngelStefan AretzMaartje NielsenGabriel CapellaDafydd Gareth EvansJohn BurnElke Holinski-federLucio BertarioBernardo BonanniAnnika LindblomZohar LeviFinlay MacraeIngrid WinshipJohn-paul PlazzerRolf SijmonsLuigi LaghiAdriana Della ValleKarl HeinimannElizabeth HalfFrancisco Lopez-koestnerKarin Alvarez-valenzuelaRodney J. ScottLior KatzIdo LaishElez VainerCarlos Alberto VaccaroDirce Maria CarraroNathan GluckNaim Abu-frehaAine StakelumRory KennellyDes WinterBenedito Mauro RossiMarc GreenblattMabel BohorquezHarsh ShethMaria Grazia TibilettiLeonardo S. Lino-silvaKaroline HorisbergerCarmen PortenkirchnerIvana NascimentoNorma Teresa RossiLeandro Apolinário Da SilvaHuw ThomasAttila ZarándJukka-pekka MecklinKirsi PylvänäinenLaura Renkonen-sinisaloAnna LepistoPäivi PeltomäkiChristina TherkildsenLars Joachim LindbergOle Thorlacius-ussingMagnus Von Knebel DoeberitzMarkus LoefflerNils RahnerVerena Steinke-langeWolff SchmiegelDeepak VangalaClaudia PerneRobert HüneburgAída Falcón De VargasAndrew LatchfordAnne-marie GerdesAnn-sofie BackmanCarmen Guillén-ponceCarrie SnyderCharlotte K. LautrupDavid AmorEdenir PalmeroElena StoffelFloor DuijkersMichael J. HallHeather HampelHeinric WilliamsHenrik OkkelsJan LubińskiJeanette ReeceJoanne NgeowJose G. GuillemJulie ArnoldKarin WadtKevin MonahanLeigha SenterLene J. RasmussenLiselotte P. Van HestLuigi RicciardielloMaija R. J. Kohonen-corishMarjolijn J. L. LigtenbergMelissa SoutheyMelyssa AronsonMohd N. ZaharyN. Jewel SamadderNicola PoplawskiNicoline HoogerbruggePatrick J. MorrisonPaul JamesGrant LeeRakefet Chen-shtoyermanRavindran AnkathilRish PaiRobyn WardSusan ParryTadeusz DębniakThomas JohnThomas Van Overeem HansenTrinidad CaldésTatsuro YamaguchiVerónica Barca-tiernoPilar GarreGiulia Martina CavestroJürgen WeitzSilke RedlerReinhard BüttnerVincent HeuvelineJohn L. HopperAung Ko WinNoralane LindorSteven GallingerLoïc Le MarchandPolly A. NewcombJane FigueiredoDaniel D. BuchananStephen N. ThibodeauSanne W. Ten BroekeEivind HovigSigve NakkenMarta PinedaNuria DueñasJoan BrunetKate GreenFiona LallooKatie NewtonEmma J. CrosbieMiriam MintsDouglas TjandraFlorencia NeffaPatricia EsperonRevital KarivGuy RosnerWalter Hernán PavicicPablo KalfayanGiovana Tardin TorrezanThiago BassanezeClaudia MartinGabriela MosleinAysel AhadovaMatthias KloorJulian R. SampsonMark A. JenkinsEuropean Hereditary Tumour GroupInternational Mismatch Repair Consortiumsubject
koloskopiaEuropean Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC)Epidemiology3122 Cancersehkäisycolorectal cancerPenetrancesegregaatioläpäisevyyssuolistosyövätGUIDELINESover-diagnosisSDG 3 - Good Health and Well-beingpreventionTumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]1112 Oncology and CarcinogenesisOncology & CarcinogenesispenetranceLynchin oireyhtymäEpidemiologiaSegregation analysisOver-diagnosiGenetics (clinical)segregation analysisScience & TechnologyIncidencePreventionColonoscòpiaGERMLINE MUTATIONSColonoscopyprospectiveCARRIERSColorectal cancer3142 Public health care science environmental and occupational healthProspectiveLynch syndromeOncologyLynch SyndromeOver-diagnosisincidence/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingCLINICAL MANAGEMENTilmaantuvuusLife Sciences & Biomedicinedescription
Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-10-01 |