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1. Genetically determined telomere length and multiple myeloma risk and outcome

Author

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, and Daniele Campa

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract 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 × 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.

Published
2021
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2. Genetically determined telomere length and multiple myeloma risk and outcome

Author

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

Subjects
0301 basic medicine, Adult, Male, MEDLINE, Library science, Myeloma, Outcome (game theory), Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Multiple myeloma, Political science, Agency (sociology), Humans, Genetic Predisposition to Disease, Prospective Studies, RC254-282, Aged, Retrospective Studies, Government, Telòmer, Mieloma múltiple, Telomere Homeostasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hematology, Middle Aged, Telomere, Prognosis, language.human_language, 030104 developmental biology, Oncology, Risk factors, 030220 oncology & carcinogenesis, language, Catalan, Female, Multiple Myeloma, Genome-Wide Association Study
Abstract

This work was partially supported by intramural funds of Univerity of Pisa and DKFZ; by Fondo de Investigaciones Sanitarias (Madrid, Spain) [PI12/02688 to J. S., PI17/02276 to J.S.]; by Instituto de Salud Carlos III, co-funded by FEDER funds —a way to build Europe—[PI14-00613 to V.M.] and by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) [2017SGR723 to V.M.]. Open Access funding enabled and organized by Projekt DEAL., 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., Univerity of Pisa, Helmholtz Association, Instituto de Salud Carlos III PI12/02688 PI17/02276, Instituto de Salud Carlos III, European Commission, FEDER funds-a way to build Europe PI14-00613, Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) 2017SGR723, Projekt DEAL

Published
2021

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