Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
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. We conducted an international...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2020
|
| In: |
Genetics in medicine
Year: 2019, Jahrgang: 22, Heft: 1, Pages: 15-25 |
| ISSN: | 1530-0366 |
| DOI: | 10.1038/s41436-019-0596-9 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1038/s41436-019-0596-9 Verlag: https://www.nature.com/articles/s41436-019-0596-9 
|
| Verfasserangaben: | Mev Dominguez-Valentin, Julian R. Sampson, Toni T. Seppälä, Sanne W. ten Broeke, John-Paul Plazzer, Sigve Nakken, Christoph Engel, Stefan Aretz, Mark A. Jenkins, Lone Sunde, Inge Bernstein, Gabriel Capella, Francesc Balaguer, Huw Thomas, D. Gareth Evans, John Burn, Marc Greenblatt, Eivind Hovig, Wouter H. de Vos tot Nederveen Cappel, Rolf H. Sijmons, Lucio Bertario, Maria Grazia Tibiletti, Giulia Martina Cavestro, Annika Lindblom, Adriana Della Valle, Francisco Lopez-Köstner, Nathan Gluck, Lior H. Katz, Karl Heinimann, Carlos A. Vaccaro, Reinhard Büttner, Heike Görgens, Elke Holinski-Feder, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Hans K. Schackert, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Karin Wadt, Christina Therkildsen, Henrik Okkels, Zohreh Ketabi, Leticia Moreira, Ariadna Sánchez, Miquel Serra-Burriel, Marta Pineda, Matilde Navarro, Ignacio Blanco, Kate Green, Fiona Lalloo, Emma J. Crosbie, James Hill, Oliver G. Denton, Ian M. Frayling, Einar Andreas Rødland, Hans Vasen, Miriam Mints, Florencia Neffa, Patricia Esperon, Karin Alvarez, Revital Kariv, Guy Rosner, Tamara Alejandra Pinero, María Laura Gonzalez, Pablo Kalfayan, Douglas Tjandra, Ingrid M. Winship, Finlay Macrae, Gabriela Möslein, Jukka-Pekka Mecklin, Maartje Nielsen, Pål Møller |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1692648969 | ||
| 003 | DE-627 | ||
| 005 | 20220818013540.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200316r20202019xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41436-019-0596-9 |2 doi | |
| 035 | |a (DE-627)1692648969 | ||
| 035 | |a (DE-599)KXP1692648969 | ||
| 035 | |a (OCoLC)1341310408 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Dominguez-Valentin, Mev |e VerfasserIn |0 (DE-588)1199455474 |0 (DE-627)1681776278 |4 aut | |
| 245 | 1 | 0 | |a Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants |b findings from the Prospective Lynch Syndrome Database |c Mev Dominguez-Valentin, Julian R. Sampson, Toni T. Seppälä, Sanne W. ten Broeke, John-Paul Plazzer, Sigve Nakken, Christoph Engel, Stefan Aretz, Mark A. Jenkins, Lone Sunde, Inge Bernstein, Gabriel Capella, Francesc Balaguer, Huw Thomas, D. Gareth Evans, John Burn, Marc Greenblatt, Eivind Hovig, Wouter H. de Vos tot Nederveen Cappel, Rolf H. Sijmons, Lucio Bertario, Maria Grazia Tibiletti, Giulia Martina Cavestro, Annika Lindblom, Adriana Della Valle, Francisco Lopez-Köstner, Nathan Gluck, Lior H. Katz, Karl Heinimann, Carlos A. Vaccaro, Reinhard Büttner, Heike Görgens, Elke Holinski-Feder, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Hans K. Schackert, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Karin Wadt, Christina Therkildsen, Henrik Okkels, Zohreh Ketabi, Leticia Moreira, Ariadna Sánchez, Miquel Serra-Burriel, Marta Pineda, Matilde Navarro, Ignacio Blanco, Kate Green, Fiona Lalloo, Emma J. Crosbie, James Hill, Oliver G. Denton, Ian M. Frayling, Einar Andreas Rødland, Hans Vasen, Miriam Mints, Florencia Neffa, Patricia Esperon, Karin Alvarez, Revital Kariv, Guy Rosner, Tamara Alejandra Pinero, María Laura Gonzalez, Pablo Kalfayan, Douglas Tjandra, Ingrid M. Winship, Finlay Macrae, Gabriela Möslein, Jukka-Pekka Mecklin, Maartje Nielsen, Pål Møller |
| 264 | 1 | |c 2020 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published: 24 July 2019 | ||
| 500 | |a Gesehen am 16.03.2020 | ||
| 520 | |a 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. 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. 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. 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. | ||
| 534 | |c 2019 | ||
| 700 | 1 | |a Knebel Doeberitz, Magnus von |e VerfasserIn |0 (DE-588)1022165291 |0 (DE-627)71693289X |0 (DE-576)364934239 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Genetics in medicine |d Amsterdam : Elsevier, 1998 |g 22(2020), 1, Seite 15-25 |h Online-Ressource |w (DE-627)338073361 |w (DE-600)2063504-7 |w (DE-576)109132475 |x 1530-0366 |7 nnas |a Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants findings from the Prospective Lynch Syndrome Database |
| 773 | 1 | 8 | |g volume:22 |g year:2020 |g number:1 |g pages:15-25 |g extent:11 |a Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants findings from the Prospective Lynch Syndrome Database |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41436-019-0596-9 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://www.nature.com/articles/s41436-019-0596-9 |x Verlag |
| 951 | |a AR | ||
| 992 | |a 20200316 | ||
| 993 | |a Article | ||
| 994 | |a 2020 | ||
| 998 | |g 1022165291 |a Knebel Doeberitz, Magnus von |m 1022165291:Knebel Doeberitz, Magnus von |d 50000 |e 50000PK1022165291 |k 0/50000/ |p 36 | ||
| 999 | |a KXP-PPN1692648969 |e 3609008571 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"physDesc":[{"extent":"11 S."}],"relHost":[{"recId":"338073361","language":["eng"],"corporate":[{"roleDisplay":"Herausgebendes Organ","display":"American College of Medical Genetics","role":"isb"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"disp":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants findings from the Prospective Lynch Syndrome DatabaseGenetics in medicine","note":["Gesehen am 27.07.2023"],"titleAlt":[{"title":"GIM"}],"part":{"issue":"1","pages":"15-25","year":"2020","extent":"11","volume":"22","text":"22(2020), 1, Seite 15-25"},"pubHistory":["1.1998/99 -"],"title":[{"subtitle":"official journal of the American College of Medical Genetics","title":"Genetics in medicine","title_sort":"Genetics in medicine"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["1530-0366"],"zdb":["2063504-7"],"eki":["338073361"]},"origin":[{"dateIssuedDisp":"1998-","publisher":"Elsevier ; Springer Nature ; Lippincott, Williams & Wilkins","dateIssuedKey":"1998","publisherPlace":"Amsterdam ; London, UK ; Baltimore, Md."}]}],"name":{"displayForm":["Mev Dominguez-Valentin, Julian R. Sampson, Toni T. Seppälä, Sanne W. ten Broeke, John-Paul Plazzer, Sigve Nakken, Christoph Engel, Stefan Aretz, Mark A. Jenkins, Lone Sunde, Inge Bernstein, Gabriel Capella, Francesc Balaguer, Huw Thomas, D. Gareth Evans, John Burn, Marc Greenblatt, Eivind Hovig, Wouter H. de Vos tot Nederveen Cappel, Rolf H. Sijmons, Lucio Bertario, Maria Grazia Tibiletti, Giulia Martina Cavestro, Annika Lindblom, Adriana Della Valle, Francisco Lopez-Köstner, Nathan Gluck, Lior H. Katz, Karl Heinimann, Carlos A. Vaccaro, Reinhard Büttner, Heike Görgens, Elke Holinski-Feder, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Hans K. Schackert, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Karin Wadt, Christina Therkildsen, Henrik Okkels, Zohreh Ketabi, Leticia Moreira, Ariadna Sánchez, Miquel Serra-Burriel, Marta Pineda, Matilde Navarro, Ignacio Blanco, Kate Green, Fiona Lalloo, Emma J. Crosbie, James Hill, Oliver G. Denton, Ian M. Frayling, Einar Andreas Rødland, Hans Vasen, Miriam Mints, Florencia Neffa, Patricia Esperon, Karin Alvarez, Revital Kariv, Guy Rosner, Tamara Alejandra Pinero, María Laura Gonzalez, Pablo Kalfayan, Douglas Tjandra, Ingrid M. Winship, Finlay Macrae, Gabriela Möslein, Jukka-Pekka Mecklin, Maartje Nielsen, Pål Møller"]},"origin":[{"dateIssuedDisp":"2020","dateIssuedKey":"2020"}],"id":{"eki":["1692648969"],"doi":["10.1038/s41436-019-0596-9"]},"note":["Published: 24 July 2019","Gesehen am 16.03.2020"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"language":["eng"],"recId":"1692648969","person":[{"given":"Mev","family":"Dominguez-Valentin","role":"aut","roleDisplay":"VerfasserIn","display":"Dominguez-Valentin, Mev"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Knebel Doeberitz, Magnus von","given":"Magnus von","family":"Knebel Doeberitz"}],"title":[{"title_sort":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants","title":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants","subtitle":"findings from the Prospective Lynch Syndrome Database"}]} | ||
| SRT | |a DOMINGUEZVCANCERRISK2020 | ||