No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2 : A Prospective Lynch Syndrome Database Study
dc.contributor.author | Dominguez-Valentin, Mev | |
dc.contributor.author | Plazzer, John-Paul | |
dc.contributor.author | Sampson, Julian R. | |
dc.contributor.author | Engel, Christoph | |
dc.contributor.author | Aretz, Stefan | |
dc.contributor.author | Jenkins, Mark A. | |
dc.contributor.author | Sunde, Lone | |
dc.contributor.author | Bernstein, Inge | |
dc.contributor.author | Capella, Gabriel | |
dc.contributor.author | Balaguer, Francesc | |
dc.contributor.author | Macrae, Finlay | |
dc.contributor.author | Winship, Ingrid M. | |
dc.contributor.author | Thomas, Huw | |
dc.contributor.author | Evans, Dafydd Gareth | |
dc.contributor.author | Burn, John | |
dc.contributor.author | Greenblatt, Marc | |
dc.contributor.author | de Vos tot Nederveen Cappel, Wouter H. | |
dc.contributor.author | Sijmons, Rolf H. | |
dc.contributor.author | Nielsen, Maartje | |
dc.contributor.author | Bertario, Lucio | |
dc.contributor.author | Bonanni, Bernardo | |
dc.contributor.author | Tibiletti, Maria Grazia | |
dc.contributor.author | Cavestro, Giulia Martina | |
dc.contributor.author | Lindblom, Annika | |
dc.contributor.author | Della Valle, Adriana | |
dc.contributor.author | Lopez-Kostner, Francisco | |
dc.contributor.author | Alvarez, Karin | |
dc.contributor.author | Gluck, Nathan | |
dc.contributor.author | Katz, Lior | |
dc.contributor.author | Heinimann, Karl | |
dc.contributor.author | Vaccaro, Carlos A. | |
dc.contributor.author | Nakken, Sigve | |
dc.contributor.author | Hovig, Eivind | |
dc.contributor.author | Green, Kate | |
dc.contributor.author | Lalloo, Fiona | |
dc.contributor.author | Hill, James | |
dc.contributor.author | Vasen, Hans F. A. | |
dc.contributor.author | Perne, Claudia | |
dc.contributor.author | Büttner, Reinhard | |
dc.contributor.author | Görgens, Heike | |
dc.contributor.author | Holinski-Feder, Elke | |
dc.contributor.author | Morak, Monika | |
dc.contributor.author | Holzapfel, Stefanie | |
dc.contributor.author | Hüneburg, Robert | |
dc.contributor.author | von Knebel Doeberitz, Magnus | |
dc.contributor.author | Loeffler, Markus | |
dc.contributor.author | Rahner, Nils | |
dc.contributor.author | Weitz, Jürgen | |
dc.contributor.author | Steinke-Lange, Verena | |
dc.contributor.author | Schmiegel, Wolff | |
dc.contributor.author | Vangala, Deepak | |
dc.contributor.author | Crosbie, Emma J. | |
dc.contributor.author | Pineda, Marta | |
dc.contributor.author | Navarro, Matilde | |
dc.contributor.author | Brunet, Joan | |
dc.contributor.author | Moreira, Leticia | |
dc.contributor.author | Sánchez, Ariadna | |
dc.contributor.author | Serra-Burriel, Miquel | |
dc.contributor.author | Mints, Miriam | |
dc.contributor.author | Kariv, Revital | |
dc.contributor.author | Rosner, Guy | |
dc.contributor.author | Piñero, Tamara Alejandra | |
dc.contributor.author | Pavicic, Walter Hernán | |
dc.contributor.author | Kalfayan, Pablo | |
dc.contributor.author | Broeke, Sanne W. ten | |
dc.contributor.author | Mecklin, Jukka-Pekka | |
dc.contributor.author | Pylvänäinen, Kirsi | |
dc.contributor.author | Renkonen-Sinisalo, Laura | |
dc.contributor.author | Lepistö, Anna | |
dc.contributor.author | Peltomäki, Päivi | |
dc.contributor.author | Hopper, John L. | |
dc.contributor.author | Win, Aung Ko | |
dc.contributor.author | Buchanan, Daniel D. | |
dc.contributor.author | Lindor, Noralane M. | |
dc.contributor.author | Gallinger, Steven | |
dc.contributor.author | Le Marchand, Loïc | |
dc.contributor.author | Newcomb, Polly A. | |
dc.contributor.author | Figueiredo, Jane C. | |
dc.contributor.author | Thibodeau, Stephen N. | |
dc.contributor.author | Therkildsen, Christina | |
dc.contributor.author | Hansen, Thomas V. O. | |
dc.contributor.author | Lindberg, Lars | |
dc.contributor.author | Rødland, Einar Andreas | |
dc.contributor.author | Neffa, Florencia | |
dc.contributor.author | Esperon, Patricia | |
dc.contributor.author | Tjandra, Douglas | |
dc.contributor.author | Möslein, Gabriela | |
dc.contributor.author | Seppälä, Toni T. | |
dc.contributor.author | Møller, Pål | |
dc.date.accessioned | 2021-07-14T06:48:12Z | |
dc.date.available | 2021-07-14T06:48:12Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Dominguez-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="https://doi.org/10.3390/jcm10132856" target="_blank">https://doi.org/10.3390/jcm10132856</a> | |
dc.identifier.other | CONVID_98997510 | |
dc.identifier.uri | https://jyx.jyu.fi/handle/123456789/77122 | |
dc.description.abstract | Background. 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.format.mimetype | application/pdf | |
dc.language.iso | eng | |
dc.publisher | MDPI AG | |
dc.relation.ispartofseries | Journal of Clinical Medicine | |
dc.rights | CC BY 4.0 | |
dc.subject.other | MLH1 | |
dc.subject.other | MSH2 | |
dc.subject.other | penetrance | |
dc.subject.other | cancer incidence | |
dc.subject.other | truncating | |
dc.subject.other | missense | |
dc.subject.other | aberrant splicing | |
dc.subject.other | Lynch syndrome | |
dc.title | No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2 : A Prospective Lynch Syndrome Database Study | |
dc.type | article | |
dc.identifier.urn | URN:NBN:fi:jyu-202107144307 | |
dc.contributor.laitos | Liikuntatieteellinen tiedekunta | fi |
dc.contributor.laitos | Faculty of Sport and Health Sciences | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | |
dc.type.coar | http://purl.org/coar/resource_type/c_2df8fbb1 | |
dc.description.reviewstatus | peerReviewed | |
dc.relation.issn | 2077-0383 | |
dc.relation.numberinseries | 13 | |
dc.relation.volume | 10 | |
dc.type.version | publishedVersion | |
dc.rights.copyright | © 2021 by the authors. | |
dc.rights.accesslevel | openAccess | fi |
dc.subject.yso | ilmaantuvuus | |
dc.subject.yso | syöpätaudit | |
dc.subject.yso | Lynchin oireyhtymä | |
dc.subject.yso | perinnölliset taudit | |
dc.subject.yso | syöpägeenit | |
dc.format.content | fulltext | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p25910 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p678 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p23697 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p19997 | |
jyx.subject.uri | http://www.yso.fi/onto/yso/p23580 | |
dc.rights.url | https://creativecommons.org/licenses/by/4.0/ | |
dc.relation.doi | 10.3390/jcm10132856 | |
jyx.fundinginformation | We 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. | |
dc.type.okm | A1 |
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