Genetically determined telomere length and multiple myeloma risk and outcome

Nom de la revue
Blood Cancer Journal
Matteo Giaccherini, Angelica Macauda, Enrico Orciuolo, Marcin Rymko, Karolina Gruenpeter, Charles Dumontet, Malgorzata Raźny, Victor Moreno, Gabriele Buda, Katia Beider, Judit Varkonyi, Hervé Avet-Loiseau, Joaquín Martinez-Lopez, Herlander Marques, Marzena Watek, Maria Eugenia Sarasquete, Vibeke Andersen, Lionel Karlin, Anna Suska, Marcin Kruszewski, Niels Abildgaard, Marek Dudziński, Aleksandra Butrym, Arnold Nagler, Annette Juul Vangsted, Katalin Kadar, Tomczak Waldemar, Krzysztof Jamroziak, Svend Erik Hove Jacobsen, Lene Hyldahl Ebbesen, Michał Taszner, Grzegorz Mazur, Fabienne Lesueur, Matteo Pelosini, Ramon Garcia-Sanz, Artur Jurczyszyn, Delphine Demangel, Rui Manuel Reis, Elżbieta Iskierka-Jażdżewska, Miroslaw Markiewicz, Federica Gemignani, Edyta Subocz, Daria Zawirska, Agnieszka Druzd-Sitek, Anna Stępień, M. Henar Alonso, Juan Sainz, Federico Canzian, Daniele Campa
Abstract

AbstractTelomeres 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 × 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.