Genetically determined telomere length and multiple myeloma risk and outcome

Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity...

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Detalles Bibliográficos
Autores: Giaccherini, Matteo, Macauda, Angelica, Orciuolo, Enrico, Rymko, Marcin, Gruenpeter, Karolina, Dumontet, Charles, Raźny, Malgorzata, Moreno Aguado, Víctor, Buda, Gabriele, Beider, Katia, Varkonyi, Judit, Avet-Loiseau, Hervé, Martínez López, Joaquín, Marques, Herlander, Watek, Marzena, Sarasquete, Maria Eugenia, Andersen, Vibeke, Karlin, Lionel, Suska, Anna, Kruszewski, Marcin, Abildgaard, Niels, Dudziński, Marek, Butrym, Aleksandra, Nagler, Arnold, Vangsted, Annette Juul, Kadar, Katalin, Waldemar, Tomczak, Jamroziak, Krzysztof, Jacobsen, Svend Erik Hove, Ebbesen, Lene Hyldahl, Taszner, Michał, Mazur, Grzegorz, Lesueur, Fabienne, Pelosini, Matteo, García Sanz, Ramón, Jurczyszyn, Artur, Demangel, Delphine, Reis, Rui Manuel, Iskierka-Jażdżewska, Elżbieta, Markiewicz, Miroslaw, Gemignani, Federica, Subocz, Edyta, Zawirska, Daria, Druzd-Sitek, Agnieszka, Stępień, Anna, Alonso Aguado, Maria Henar, Sainz, Juan, Canzian, Federico, Campa, Daniele
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/177059
Acceso en línea:https://hdl.handle.net/2445/177059
Access Level:acceso abierto
Palabra clave:Mieloma múltiple
Telòmer
Multiple myeloma
Telomere
Descripción
Sumario:Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the "teloscore" in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36-2.11; P = 2.97 x 10(-6) for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86-0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.

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