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dc.contributor.authorDominguez-Valentin, Mev
dc.contributor.authorPlazzer, John-Paul
dc.contributor.authorSampson, Julian R.
dc.contributor.authorEngel, Christoph
dc.contributor.authorAretz, Stefan
dc.contributor.authorJenkins, Mark A.
dc.contributor.authorSunde, Lone
dc.contributor.authorBernstein, Inge
dc.contributor.authorCapella, Gabriel
dc.contributor.authorBalaguer, Francesc
dc.contributor.authorMacrae, Finlay
dc.contributor.authorWinship, Ingrid M.
dc.contributor.authorThomas, Huw
dc.contributor.authorEvans, Dafydd Gareth
dc.contributor.authorBurn, John
dc.contributor.authorGreenblatt, Marc
dc.contributor.authorde Vos tot Nederveen Cappel, Wouter H.
dc.contributor.authorSijmons, Rolf H.
dc.contributor.authorNielsen, Maartje
dc.contributor.authorBertario, Lucio
dc.contributor.authorBonanni, Bernardo
dc.contributor.authorTibiletti, Maria Grazia
dc.contributor.authorCavestro, Giulia Martina
dc.contributor.authorLindblom, Annika
dc.contributor.authorDella Valle, Adriana
dc.contributor.authorLopez-Kostner, Francisco
dc.contributor.authorAlvarez, Karin
dc.contributor.authorGluck, Nathan
dc.contributor.authorKatz, Lior
dc.contributor.authorHeinimann, Karl
dc.contributor.authorVaccaro, Carlos A.
dc.contributor.authorNakken, Sigve
dc.contributor.authorHovig, Eivind
dc.contributor.authorGreen, Kate
dc.contributor.authorLalloo, Fiona
dc.contributor.authorHill, James
dc.contributor.authorVasen, Hans F. A.
dc.contributor.authorPerne, Claudia
dc.contributor.authorBüttner, Reinhard
dc.contributor.authorGörgens, Heike
dc.contributor.authorHolinski-Feder, Elke
dc.contributor.authorMorak, Monika
dc.contributor.authorHolzapfel, Stefanie
dc.contributor.authorHüneburg, Robert
dc.contributor.authorvon Knebel Doeberitz, Magnus
dc.contributor.authorLoeffler, Markus
dc.contributor.authorRahner, Nils
dc.contributor.authorWeitz, Jürgen
dc.contributor.authorSteinke-Lange, Verena
dc.contributor.authorSchmiegel, Wolff
dc.contributor.authorVangala, Deepak
dc.contributor.authorCrosbie, Emma J.
dc.contributor.authorPineda, Marta
dc.contributor.authorNavarro, Matilde
dc.contributor.authorBrunet, Joan
dc.contributor.authorMoreira, Leticia
dc.contributor.authorSánchez, Ariadna
dc.contributor.authorSerra-Burriel, Miquel
dc.contributor.authorMints, Miriam
dc.contributor.authorKariv, Revital
dc.contributor.authorRosner, Guy
dc.contributor.authorPiñero, Tamara Alejandra
dc.contributor.authorPavicic, Walter Hernán
dc.contributor.authorKalfayan, Pablo
dc.contributor.authorBroeke, Sanne W. ten
dc.contributor.authorMecklin, Jukka-Pekka
dc.contributor.authorPylvänäinen, Kirsi
dc.contributor.authorRenkonen-Sinisalo, Laura
dc.contributor.authorLepistö, Anna
dc.contributor.authorPeltomäki, Päivi
dc.contributor.authorHopper, John L.
dc.contributor.authorWin, Aung Ko
dc.contributor.authorBuchanan, Daniel D.
dc.contributor.authorLindor, Noralane M.
dc.contributor.authorGallinger, Steven
dc.contributor.authorLe Marchand, Loïc
dc.contributor.authorNewcomb, Polly A.
dc.contributor.authorFigueiredo, Jane C.
dc.contributor.authorThibodeau, Stephen N.
dc.contributor.authorTherkildsen, Christina
dc.contributor.authorHansen, Thomas V. O.
dc.contributor.authorLindberg, Lars
dc.contributor.authorRødland, Einar Andreas
dc.contributor.authorNeffa, Florencia
dc.contributor.authorEsperon, Patricia
dc.contributor.authorTjandra, Douglas
dc.contributor.authorMöslein, Gabriela
dc.contributor.authorSeppälä, Toni T.
dc.contributor.authorMøller, Pål
dc.identifier.citationDominguez-Valentin, M., Plazzer, J.-P., Sampson, J. R., Engel, C., Aretz, S., Jenkins, M. A., Sunde, L., Bernstein, I., Capella, G., Balaguer, F., Macrae, F., Winship, I. M., Thomas, H., Evans, D. G., Burn, J., Greenblatt, M., de Vos tot Nederveen Cappel, W. H., Sijmons, R. H., Nielsen, M., . . . Møller, P. (2021). No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2 : A Prospective Lynch Syndrome Database Study. <i>Journal of Clinical Medicine</i>, <i>10</i>(13), Article 2856. <a href="" target="_blank"></a>
dc.description.abstractBackground. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.en
dc.publisherMDPI AG
dc.relation.ispartofseriesJournal of Clinical Medicine
dc.rightsCC BY 4.0
dc.subject.othercancer incidence
dc.subject.otheraberrant splicing
dc.subject.otherLynch syndrome
dc.titleNo Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2 : A Prospective Lynch Syndrome Database Study
dc.contributor.laitosLiikuntatieteellinen tiedekuntafi
dc.contributor.laitosFaculty of Sport and Health Sciencesen
dc.rights.copyright© 2021 by the authors.
dc.subject.ysoLynchin oireyhtymä
dc.subject.ysoperinnölliset taudit
jyx.fundinginformationWe acknowledge funding from the Norwegian Cancer Society, contract 194751-2017. The Colon CFR is supported in part by the National Cancer Institute of the National Institutes of Health under Award Number UM1CA167551. The Finnish contribution: Cancer Foundation Finland, Jane and Aatos Erkko Foundation, Emil Aaltonen Foundation, Finnish Medical Foundation, Sigrid Juselius Foundation, Instrumentarium Science Foundation, iCAN Flagship of the Academy of Finland. D.G.E. and E.J.C. are supported by the Manchester National Institute for Health Research (NIHR) Biomedical Research Centre (IS-BRC-1215-20007). The contribution from Wales was supported by the Wales Gene Park award from Health and Care Research Wales. The German Consortium for Familial Intestinal Cancer was supported by grants from the German Cancer Aid. Work by G.C., M.N., J.B., and M.P. was funded by the Spanish Ministry of Science and Innovation and cofounded by FEDER M.D. Catalonia (grants 2017SGR1282). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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