Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/179425
Title: No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
Author: Dominguez Valentin, Mev
Plazzer, John Paul
Sampson, Julian R.
Engel, Christoph
Aretz, Stefan
Jenkins, Mark A.
Sunde, Lone
Bernstein, Inge
Capellá, G. (Gabriel)
Balaguer Prunés, Francesc
Macrae, Finlay
Winship, Ingrid M.
Thomas, Huw
Evans, Dafydd Gareth
Burn, John
Greenblatt, Marc
de Vos Tot Nederveen Cappel, Wouter H.
Sijmons, Rolf H.
Nielsen, Maartje
Bertario, Lucio
Bonanni, Bernardo
Tibiletti, Maria Grazia
Cavestro, Giulia Martina
Lindblom, Annika
Valle, Adriana Della
Lopez Kostner, Francisco
Alvarez, Karin
Gluck, Nathan
Katz, Lior
Heinimann, Karl
Vaccaro, Carlos A.
Nakken, Sigve
Hovig, Eivind
Green, Kate
Lalloo, Fiona
Hill, James
Vasen, Hans F. A.
Perne, Claudia
Büttner, Reinhard
Görgens, Heike
Holinski Feder, Elke
Morak, Monika
Holzapfel, Stefanie
Hüneburg, Robert
von Knebel Doeberitz, Magnus
Loeffler, Markus
Rahner, Nils
Weitz, Jürgen
Steinke Lange, Verena
Schmiegel, Wolff
Vangala, Deepak
Crosbie, Emma J.
Pineda, Marta
Navarro, Matilde
Brunet, Joan
Moreira, Leticia
Sánchez, Ariadna
Serra Burriel, Miquel
Mints, Miriam
Kariv, Revital
Rosner, Guy
Piñero, Tamara Alejandra
Pavicic, Walter Hernán
Kalfayan, Pablo
ten Broeke, Sanne W.
Mecklin, Jukka-Pekka
Pylvänäinen, Kirsi
Renkonen Sinisalo, Laura
Lepistö, Anna
Peltomäki, Päivi
Hopper, John L.
Ko Win, Aung
Buchanan, Daniel D.
Lindor, Noralane M.
Gallinger, Steven
Le Marchand, Loïc
Newcomb, Polly A.
Figueiredo, Jane C.
Thibodeau, Stephen N.
Therkildsen, Christina
Hansen, Thomas V. O.
Lindberg, Lars
Rødland, Einar Andreas
Neffa, Florencia
Esperon, Patricia
Tjandra, Douglas
Möslein, Gabriela
Seppälä, Toni T.
Møller, Pål
Keywords: Càncer
Malalties hereditàries
Factors de risc en les malalties
Cancer
Genetic diseases
Risk factors in diseases
Issue Date: 28-Jun-2021
Publisher: MDPI
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.
Note: Reproducció del document publicat a: https://doi.org/10.3390/jcm10132856
It is part of: Journal of Clinical Medicine, 2021, vol. 10, num. 13, p. 2856
URI: http://hdl.handle.net/2445/179425
Related resource: https://doi.org/10.3390/jcm10132856
ISSN: 2077-0383
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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