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dc.date.accessioned2020-05-22T19:31:50Z
dc.date.available2020-05-22T19:31:50Z
dc.date.created2020-01-06T21:07:00Z
dc.date.issued2020
dc.identifier.citationDominguez-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.urihttp://hdl.handle.net/10852/76121
dc.description.abstractPurpose 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.languageEN
dc.publisherLippincott Williams & Wilkins
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.titleCancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
dc.typeJournal article
dc.creator.authorDominguez-Valentin, Mev
dc.creator.authorSampson, Julian R.
dc.creator.authorSeppälä, Toni T.
dc.creator.authorten Broeke, Sanne W.
dc.creator.authorPlazzer, John-Paul
dc.creator.authorNakken, Sigve
dc.creator.authorEngel, Christoph
dc.creator.authorAretz, Stefan
dc.creator.authorJenkins, Mark A.
dc.creator.authorSunde, Lone
dc.creator.authorBernstein, Inge
dc.creator.authorCapella, Gabriel
dc.creator.authorBalaguer, Francesc
dc.creator.authorThomas, Huw
dc.creator.authorEvans, D. Gareth
dc.creator.authorBurn, John
dc.creator.authorGreenblatt, Marc
dc.creator.authorHovig, Eivind
dc.creator.authorde Vos tot Nederveen Cappel, Wouter H.
dc.creator.authorSijmons, Rolf H.
dc.creator.authorBertario, Lucio
dc.creator.authorTibiletti, Maria Grazia
dc.creator.authorCavestro, Giulia Martina
dc.creator.authorLindblom, Annika
dc.creator.authorDella Valle, Adriana
dc.creator.authorLópez-Köstner, Francisco
dc.creator.authorGluck, Nathan
dc.creator.authorKatz, Lior H.
dc.creator.authorHeinimann, Karl
dc.creator.authorVaccaro, Carlos A.
dc.creator.authorBüttner, Reinhard
dc.creator.authorGörgens, Heike
dc.creator.authorHolinski-Feder, Elke
dc.creator.authorMorak, Monika
dc.creator.authorHolzapfel, Stefanie
dc.creator.authorHüneburg, Robert
dc.creator.authorvon Knebel Doeberitz, Magnus
dc.creator.authorLoeffler, Markus
dc.creator.authorRahner, Nils
dc.creator.authorSchackert, Hans K.
dc.creator.authorSteinke-Lange, Verena
dc.creator.authorSchmiegel, Wolff
dc.creator.authorVangala, Deepak
dc.creator.authorPylvänäinen, Kirsi
dc.creator.authorRenkonen-Sinisalo, Laura
dc.creator.authorHopper, John L.
dc.creator.authorWin, Aung Ko
dc.creator.authorHaile, Robert W.
dc.creator.authorLindor, Noralane M.
dc.creator.authorGallinger, Steven
dc.creator.authorLe Marchand, Loïc
dc.creator.authorNewcomb, Polly A.
dc.creator.authorFigueiredo, Jane C.
dc.creator.authorThibodeau, Stephen N.
dc.creator.authorWadt, Karin
dc.creator.authorTherkildsen, Christina
dc.creator.authorOkkels, Henrik
dc.creator.authorKetabi, Zohreh
dc.creator.authorMoreira, Leticia
dc.creator.authorSánchez, Ariadna
dc.creator.authorSerra-Burriel, Miquel
dc.creator.authorPineda, Marta
dc.creator.authorNavarro, Matilde
dc.creator.authorBlanco, Ignacio
dc.creator.authorGreen, Kate
dc.creator.authorLalloo, Fiona
dc.creator.authorCrosbie, Emma J.
dc.creator.authorHill, James
dc.creator.authorDenton, Oliver G.
dc.creator.authorFrayling, Ian M.
dc.creator.authorRødland, Einar Andreas
dc.creator.authorVasen, Hans
dc.creator.authorMints, Miriam
dc.creator.authorNeffa, Florencia
dc.creator.authorEsperon, Patricia
dc.creator.authorAlvarez, Karin
dc.creator.authorKariv, Revital
dc.creator.authorRosner, Guy
dc.creator.authorPinero, Tamara Alejandra
dc.creator.authorGonzalez, Maria Laura
dc.creator.authorKalfayan, Pablo
dc.creator.authorTjandra, Douglas
dc.creator.authorWinship, Ingrid M.
dc.creator.authorMacrae, Finlay
dc.creator.authorMöslein, Gabriela
dc.creator.authorMecklin, Jukka-Pekka
dc.creator.authorNielsen, Maartje
dc.creator.authorMøller, Pål
cristin.unitcode185,53,2,15
cristin.unitnameSenter for kreftcelle-reprogrammering
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1767240
dc.identifier.bibliographiccitationinfo: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.jtitleGenetics in Medicine
dc.identifier.volume22
dc.identifier.issue1
dc.identifier.startpage15
dc.identifier.endpage25
dc.identifier.doihttps://doi.org/10.1038/s41436-019-0596-9
dc.identifier.urnURN:NBN:no-79213
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn1098-3600
dc.identifier.fulltextFulltext 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.versionPublishedVersion
dc.relation.projectKF/Contract:194751-2017


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