Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

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dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor.author Dominguez-Valentin, Mev
dc.contributor.author Sampson, Julian R
dc.contributor.author Seppälä, Toni T
dc.contributor.author Ten Broeke, Sanne W
dc.contributor.author Plazzer, John-Paul
dc.contributor.author Nakken, Sigve
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 Thomas, Huw
dc.contributor.author Evans, D Gareth
dc.contributor.author Burn, John
dc.contributor.author Greenblatt, Marc
dc.contributor.author Hovig, Eivind
dc.contributor.author de Vos Tot Nederveen Cappel, Wouter H
dc.contributor.author Sijmons, Rolf H
dc.contributor.author Bertario, Lucio
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-Köstner, Francisco
dc.contributor.author Gluck, Nathan
dc.contributor.author Katz, Lior H
dc.contributor.author Heinimann, Karl
dc.contributor.author Vaccaro, Carlos A
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 Knebel Doeberitz, Magnus von
dc.contributor.author Loeffler, Markus
dc.contributor.author Rahner, Nils
dc.contributor.author Schackert, Hans K
dc.contributor.author Steinke-Lange, Verena
dc.contributor.author Schmiegel, Wolff
dc.contributor.author Vangala, Deepak
dc.contributor.author Pylvänäinen, Kirsi
dc.contributor.author Renkonen-Sinisalo, Laura
dc.contributor.author Hopper, John L
dc.contributor.author Win, Aung Ko
dc.contributor.author Haile, Robert W
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 Wadt, Karin
dc.contributor.author Therkildsen, Christina
dc.contributor.author Okkels, Henrik
dc.contributor.author Ketabi, Zohreh
dc.contributor.author Moreira, Leticia
dc.contributor.author Sánchez, Ariadna
dc.contributor.author Serra-Burriel, Miquel
dc.contributor.author Pineda, Marta
dc.contributor.author Navarro, Matilde
dc.contributor.author Blanco, Ignacio
dc.contributor.author Green, Kate
dc.contributor.author Lalloo, Fiona
dc.contributor.author Crosbie, Emma J
dc.contributor.author Hill, James
dc.contributor.author Denton, Oliver G
dc.contributor.author Frayling, Ian M
dc.contributor.author Rødland, Einar Andreas
dc.contributor.author Vasen, Hans
dc.contributor.author Mints, Miriam
dc.contributor.author Neffa, Florencia
dc.contributor.author Esperon, Patricia
dc.contributor.author Alvarez, Karin
dc.contributor.author Kariv, Revital
dc.contributor.author Rosner, Guy
dc.contributor.author Pinero, Tamara Alejandra
dc.contributor.author Gonzalez, María Laura
dc.contributor.author Kalfayan, Pablo
dc.contributor.author Tjandra, Douglas
dc.contributor.author Winship, Ingrid M
dc.contributor.author Macrae, Finlay
dc.contributor.author Möslein, Gabriela
dc.contributor.author Mecklin, Jukka-Pekka
dc.contributor.author Nielsen, Maartje
dc.contributor.author Møller, Pål
dc.date.accessioned 2020-02-03T14:56:01Z
dc.date.available 2020-02-03T14:56:01Z
dc.date.issued 2020-01
dc.identifier.citation Dominguez-Valentin , M , Sampson , J R , Seppälä , T T , Ten Broeke , S W , Plazzer , J-P , Nakken , S , Engel , C , Aretz , S , Jenkins , M A , Sunde , L , Bernstein , I , Capella , G , Balaguer , F , Thomas , H , Evans , D G , Burn , J , Greenblatt , M , Hovig , E , de Vos Tot Nederveen Cappel , W H , Sijmons , R H , Bertario , L , Tibiletti , M G , Cavestro , G M , Lindblom , A , Della Valle , A , Lopez-Köstner , F , Gluck , N , Katz , L H , Heinimann , K , Vaccaro , C A , Büttner , R , Görgens , H , Holinski-Feder , E , Morak , M , Holzapfel , S , Hüneburg , R , Knebel Doeberitz , M V , Loeffler , M , Rahner , N , Schackert , H K , Steinke-Lange , V , Schmiegel , W , Vangala , D , Pylvänäinen , K , Renkonen-Sinisalo , L , Hopper , J L , Win , A K , Haile , R W , Lindor , N M , Gallinger , S , Le Marchand , L , Newcomb , P A , Figueiredo , J C , Thibodeau , S N , Wadt , K , Therkildsen , C , Okkels , H , Ketabi , Z , Moreira , L , Sánchez , A , Serra-Burriel , M , Pineda , M , Navarro , M , Blanco , I , Green , K , Lalloo , F , Crosbie , E J , Hill , J , Denton , O G , Frayling , I M , Rødland , E A , Vasen , H , Mints , M , Neffa , F , Esperon , P , Alvarez , K , Kariv , R , Rosner , G , Pinero , T A , Gonzalez , M L , Kalfayan , P , Tjandra , D , Winship , I M , Macrae , F , Möslein , G , Mecklin , J-P , Nielsen , M & Møller , P 2020 , ' 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 , vol. 22 , no. 1 , pp. 15-25 . https://doi.org/10.1038/s41436-019-0596-9 en
dc.identifier.issn 1098-3600
dc.identifier.other PURE: 131339642
dc.identifier.other PURE UUID: 0533e782-d00e-4b03-8b3e-06190cccdef5
dc.identifier.other RIS: urn:19DE53ECC1647D9810B5D93668072CD0
dc.identifier.other ORCID: /0000-0002-4940-3498/work/68617630
dc.identifier.other WOS: 000510943400005
dc.identifier.uri http://hdl.handle.net/10138/310917
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. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof Genetics In medicine
dc.rights en
dc.subject *Lynch syndrome en
dc.subject *MLH1 en
dc.subject *MSH2 en
dc.subject *MSH6 en
dc.subject *PMS2 en
dc.subject 1184 Genetics, developmental biology, physiology en
dc.subject 3111 Biomedicine en
dc.title Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/s41436-019-0596-9
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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