Blood Cancer Journal (Apr 2021)
Genetically determined telomere length and multiple myeloma risk and outcome
- 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
Affiliations
- Matteo Giaccherini
- Department of Biology, University of Pisa
- Angelica Macauda
- Department of Biology, University of Pisa
- Enrico Orciuolo
- Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa
- Marcin Rymko
- Department of Hematology, Copernicus Hospital
- Karolina Gruenpeter
- Department of Haematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia
- Charles Dumontet
- Hospices Civils de Lyon
- Malgorzata Raźny
- Department of Hematology, Rydygier Specialistic Hospital
- Victor Moreno
- Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona
- Gabriele Buda
- Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa
- Katia Beider
- Hematology Division, Chaim Sheba Medical Center
- Judit Varkonyi
- Semmelweis University
- Hervé Avet-Loiseau
- Laboratory for Genomics in Myeloma, Institut Universitaire du Cancer and University Hospital, Centre de Recherche en Cancerologie de Toulouse
- Joaquín Martinez-Lopez
- Hospital 12 de Octubre, Complentese University, CNIO, CIBERONC
- Herlander Marques
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B’s – PT Government Associate Laboratory
- Marzena Watek
- Department of Hematology, Holy Cross Cancer Center
- Maria Eugenia Sarasquete
- Hematology Department, University Hospital of Salamanca, CIBERONC
- Vibeke Andersen
- Department of Biochemistry, University Hospital of Southern Jutland
- Lionel Karlin
- Hospices Civils de Lyon
- Anna Suska
- Department of Hematology, Jagiellonian University Medical College
- Marcin Kruszewski
- Department of Hematology, University Hospital No. 2 in Bydgoszcz
- Niels Abildgaard
- Department of Hematology, Odense University Hospital
- Marek Dudziński
- Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow
- Aleksandra Butrym
- Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University
- Arnold Nagler
- Hematology Division, Chaim Sheba Medical Center
- Annette Juul Vangsted
- Department of Hematology, Rigshospitalet
- Katalin Kadar
- Semmelweis University
- Tomczak Waldemar
- Department of Haemato-oncology and Bone Marrow Transplantation and Department of Internal Medicine in Nursing, Medical University of Lublin
- Krzysztof Jamroziak
- Department of Hematology, Institute of Hematology and Transfusion Medicine
- Svend Erik Hove Jacobsen
- Department of Biochemistry, University Hospital of Southern Jutland
- Lene Hyldahl Ebbesen
- Department of Hematology, Aarhus University Hospital
- Michał Taszner
- Department of Hematology and Transplantology Medical University of Gdansk
- Grzegorz Mazur
- Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University
- Fabienne Lesueur
- Inserm, U900, Institut Curie, PSL University
- Matteo Pelosini
- U.O. Dipartimento di Ematologia, Azienda USL Toscana Nord Ovest, Livorno, Italy, currently Ospedale Santa Chiara
- Ramon Garcia-Sanz
- Hematology Department, University Hospital of Salamanca, CIBERONC
- Artur Jurczyszyn
- Department of Hematology, Jagiellonian University Medical College
- Delphine Demangel
- Hospices Civils de Lyon
- Rui Manuel Reis
- Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B’s – PT Government Associate Laboratory
- Elżbieta Iskierka-Jażdżewska
- Department of Hematology, Medical University of Lodz
- Miroslaw Markiewicz
- Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow
- Federica Gemignani
- Department of Biology, University of Pisa
- Edyta Subocz
- Department of Hematology, Military Institute of Medicine
- Daria Zawirska
- Department of Haematology, University Hospital in Cracow
- Agnieszka Druzd-Sitek
- Department of Lymphoid Malignancies, Maria Skłodowska-Curie National Research Institute of Oncology
- Anna Stępień
- Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital
- M. Henar Alonso
- Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona
- Juan Sainz
- Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government
- Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
- Daniele Campa
- Department of Biology, University of Pisa
- DOI
- https://doi.org/10.1038/s41408-021-00462-y
- Journal volume & issue
-
Vol. 11,
no. 4
pp. 1 – 10
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.