Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
dc.date.accessioned | 2020-05-22T19:31:50Z | |
dc.date.available | 2020-05-22T19:31:50Z | |
dc.date.created | 2020-01-06T21:07:00Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Dominguez-Valentin, Mev Sampson, Julian R. Seppälä, Toni T. ten Broeke, Sanne W. Plazzer, John-Paul Nakken, Sigve Engel, Christoph Aretz, Stefan Jenkins, Mark A. Sunde, Lone Bernstein, Inge Capella, Gabriel Balaguer, Francesc Thomas, Huw Evans, D. Gareth Burn, John Greenblatt, Marc Hovig, Eivind de Vos tot Nederveen Cappel, Wouter H. Sijmons, Rolf H. Bertario, Lucio Tibiletti, Maria Grazia Cavestro, Giulia Martina Lindblom, Annika Della Valle, Adriana López-Köstner, Francisco Gluck, Nathan Katz, Lior H. Heinimann, Karl Vaccaro, Carlos A. Büttner, Reinhard Görgens, Heike Holinski-Feder, Elke Morak, Monika Holzapfel, Stefanie Hüneburg, Robert von Knebel Doeberitz, Magnus Loeffler, Markus Rahner, Nils Schackert, Hans K. Steinke-Lange, Verena Schmiegel, Wolff Vangala, Deepak Pylvänäinen, Kirsi Renkonen-Sinisalo, Laura Hopper, John L. Win, Aung Ko Haile, Robert W. Lindor, Noralane M. Gallinger, Steven Le Marchand, Loïc Newcomb, Polly A. Figueiredo, Jane C. Thibodeau, Stephen N. Wadt, Karin Therkildsen, Christina Okkels, Henrik Ketabi, Zohreh Moreira, Leticia Sánchez, Ariadna Serra-Burriel, Miquel Pineda, Marta Navarro, Matilde Blanco, Ignacio Green, Kate Lalloo, Fiona Crosbie, Emma J. Hill, James Denton, Oliver G. Frayling, Ian M. Rødland, Einar Andreas Vasen, Hans Mints, Miriam Neffa, Florencia Esperon, Patricia Alvarez, Karin Kariv, Revital Rosner, Guy Pinero, Tamara Alejandra Gonzalez, Maria Laura Kalfayan, Pablo Tjandra, Douglas Winship, Ingrid M. Macrae, Finlay Möslein, Gabriela Mecklin, Jukka-Pekka Nielsen, Maartje Møller, Pål . Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genetics in Medicine. 2019, 22, 15-25 | |
dc.identifier.uri | http://hdl.handle.net/10852/76121 | |
dc.description.abstract | Purpose Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. Methods We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. Results There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. Conclusion Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers. | |
dc.language | EN | |
dc.publisher | Lippincott Williams & Wilkins | |
dc.rights | Attribution-NonCommercial-ShareAlike 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/4.0/ | |
dc.title | Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database | |
dc.type | Journal article | |
dc.creator.author | Dominguez-Valentin, Mev | |
dc.creator.author | Sampson, Julian R. | |
dc.creator.author | Seppälä, Toni T. | |
dc.creator.author | ten Broeke, Sanne W. | |
dc.creator.author | Plazzer, John-Paul | |
dc.creator.author | Nakken, Sigve | |
dc.creator.author | Engel, Christoph | |
dc.creator.author | Aretz, Stefan | |
dc.creator.author | Jenkins, Mark A. | |
dc.creator.author | Sunde, Lone | |
dc.creator.author | Bernstein, Inge | |
dc.creator.author | Capella, Gabriel | |
dc.creator.author | Balaguer, Francesc | |
dc.creator.author | Thomas, Huw | |
dc.creator.author | Evans, D. Gareth | |
dc.creator.author | Burn, John | |
dc.creator.author | Greenblatt, Marc | |
dc.creator.author | Hovig, Eivind | |
dc.creator.author | de Vos tot Nederveen Cappel, Wouter H. | |
dc.creator.author | Sijmons, Rolf H. | |
dc.creator.author | Bertario, Lucio | |
dc.creator.author | Tibiletti, Maria Grazia | |
dc.creator.author | Cavestro, Giulia Martina | |
dc.creator.author | Lindblom, Annika | |
dc.creator.author | Della Valle, Adriana | |
dc.creator.author | López-Köstner, Francisco | |
dc.creator.author | Gluck, Nathan | |
dc.creator.author | Katz, Lior H. | |
dc.creator.author | Heinimann, Karl | |
dc.creator.author | Vaccaro, Carlos A. | |
dc.creator.author | Büttner, Reinhard | |
dc.creator.author | Görgens, Heike | |
dc.creator.author | Holinski-Feder, Elke | |
dc.creator.author | Morak, Monika | |
dc.creator.author | Holzapfel, Stefanie | |
dc.creator.author | Hüneburg, Robert | |
dc.creator.author | von Knebel Doeberitz, Magnus | |
dc.creator.author | Loeffler, Markus | |
dc.creator.author | Rahner, Nils | |
dc.creator.author | Schackert, Hans K. | |
dc.creator.author | Steinke-Lange, Verena | |
dc.creator.author | Schmiegel, Wolff | |
dc.creator.author | Vangala, Deepak | |
dc.creator.author | Pylvänäinen, Kirsi | |
dc.creator.author | Renkonen-Sinisalo, Laura | |
dc.creator.author | Hopper, John L. | |
dc.creator.author | Win, Aung Ko | |
dc.creator.author | Haile, Robert W. | |
dc.creator.author | Lindor, Noralane M. | |
dc.creator.author | Gallinger, Steven | |
dc.creator.author | Le Marchand, Loïc | |
dc.creator.author | Newcomb, Polly A. | |
dc.creator.author | Figueiredo, Jane C. | |
dc.creator.author | Thibodeau, Stephen N. | |
dc.creator.author | Wadt, Karin | |
dc.creator.author | Therkildsen, Christina | |
dc.creator.author | Okkels, Henrik | |
dc.creator.author | Ketabi, Zohreh | |
dc.creator.author | Moreira, Leticia | |
dc.creator.author | Sánchez, Ariadna | |
dc.creator.author | Serra-Burriel, Miquel | |
dc.creator.author | Pineda, Marta | |
dc.creator.author | Navarro, Matilde | |
dc.creator.author | Blanco, Ignacio | |
dc.creator.author | Green, Kate | |
dc.creator.author | Lalloo, Fiona | |
dc.creator.author | Crosbie, Emma J. | |
dc.creator.author | Hill, James | |
dc.creator.author | Denton, Oliver G. | |
dc.creator.author | Frayling, Ian M. | |
dc.creator.author | Rødland, Einar Andreas | |
dc.creator.author | Vasen, Hans | |
dc.creator.author | Mints, Miriam | |
dc.creator.author | Neffa, Florencia | |
dc.creator.author | Esperon, Patricia | |
dc.creator.author | Alvarez, Karin | |
dc.creator.author | Kariv, Revital | |
dc.creator.author | Rosner, Guy | |
dc.creator.author | Pinero, Tamara Alejandra | |
dc.creator.author | Gonzalez, Maria Laura | |
dc.creator.author | Kalfayan, Pablo | |
dc.creator.author | Tjandra, Douglas | |
dc.creator.author | Winship, Ingrid M. | |
dc.creator.author | Macrae, Finlay | |
dc.creator.author | Möslein, Gabriela | |
dc.creator.author | Mecklin, Jukka-Pekka | |
dc.creator.author | Nielsen, Maartje | |
dc.creator.author | Møller, Pål | |
cristin.unitcode | 185,53,2,15 | |
cristin.unitname | Senter for kreftcelle-reprogrammering | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1767240 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Genetics in Medicine&rft.volume=22&rft.spage=15&rft.date=2019 | |
dc.identifier.jtitle | Genetics in Medicine | |
dc.identifier.volume | 22 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | 15 | |
dc.identifier.endpage | 25 | |
dc.identifier.doi | https://doi.org/10.1038/s41436-019-0596-9 | |
dc.identifier.urn | URN:NBN:no-79213 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1098-3600 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/76121/1/Cancer%2Brisks%2Bby%2Bgene%252C%2Bage%252C%2Band%2Bgender%2Bin%2B6350%2Bcarriers%2Bof%2Bpathogenic%2Bmismatch%2Brepair%2Bvariants%2B-%2Bfindings%2Bfrom%2Bthe%2BProspective%2BLynch%2BSyndrome%2BDatabase.pdf | |
dc.type.version | PublishedVersion | |
dc.relation.project | KF/Contract:194751-2017 |
Tilhørende fil(er)
Finnes i følgende samling
-
Institutt for klinisk medisin [10783]
-
CRIStin høstingsarkiv [31417]