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.

Details

Title
Genetically determined telomere length and multiple myeloma risk and outcome
Author
Giaccherini Matteo 1   VIAFID ORCID Logo  ; Macauda Angelica 2 ; Orciuolo Enrico 3 ; Rymko Marcin 4 ; Gruenpeter Karolina 5 ; Dumontet, Charles 6 ; Raźny Malgorzata 7 ; Moreno, Victor 8   VIAFID ORCID Logo  ; Buda Gabriele 3 ; Beider Katia 9 ; Varkonyi Judit 10 ; Avet-Loiseau Hervé 11 ; Martinez-Lopez, Joaquín 12   VIAFID ORCID Logo  ; Marques Herlander 13 ; Watek Marzena 14 ; Sarasquete Maria Eugenia 15   VIAFID ORCID Logo  ; Andersen, Vibeke 16 ; Karlin, Lionel 6 ; Suska, Anna 17 ; Kruszewski Marcin 18 ; Abildgaard Niels 19 ; Dudziński Marek 20 ; Butrym Aleksandra 21 ; Nagler, Arnold 9 ; Vangsted, Annette Juul 22   VIAFID ORCID Logo  ; Kadar Katalin 10 ; Tomczak, Waldemar 23   VIAFID ORCID Logo  ; Jamroziak Krzysztof 24 ; Jacobsen Svend Erik Hove 25 ; Ebbesen, Lene Hyldahl 26 ; Taszner Michał 27   VIAFID ORCID Logo  ; Mazur Grzegorz 21   VIAFID ORCID Logo  ; Lesueur Fabienne 28 ; Pelosini Matteo 29 ; Garcia-Sanz, Ramon 15   VIAFID ORCID Logo  ; Jurczyszyn Artur 17   VIAFID ORCID Logo  ; Demangel Delphine 6 ; Reis, Rui Manuel 30 ; Iskierka-Jażdżewska Elżbieta 31 ; Markiewicz Miroslaw 20   VIAFID ORCID Logo  ; Gemignani Federica 1 ; Subocz Edyta 32 ; Zawirska Daria 33 ; Druzd-Sitek Agnieszka 34 ; Stępień, Anna 35 ; Henar, Alonso M 8 ; Sainz, Juan 36   VIAFID ORCID Logo  ; Canzian Federico 37   VIAFID ORCID Logo  ; Campa Daniele 1 

1  University of Pisa, Department of Biology, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729) 
2  University of Pisa, Department of Biology, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729); German Cancer Research Center (DKFZ), Genomic Epidemiology Group, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
3  University of Pisa, Haematology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy (GRID:grid.5395.a) (ISNI:0000 0004 1757 3729) 
4  Copernicus Hospital, Department of Hematology, Torun, Poland (GRID:grid.5395.a) 
5  Medical University of Silesia, Department of Haematology and Bone Marrow Transplantation, School of Medicine in Katowice, Katowice, Poland (GRID:grid.411728.9) (ISNI:0000 0001 2198 0923) 
6  Hospices Civils de Lyon, Lyon, France (GRID:grid.413852.9) (ISNI:0000 0001 2163 3825) 
7  Rydygier Specialistic Hospital, Department of Hematology, Cracow, Poland (GRID:grid.413852.9) 
8  University of Barcelona, Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247) 
9  Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel (GRID:grid.413795.d) (ISNI:0000 0001 2107 2845) 
10  Semmelweis University, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821) 
11  Laboratory for Genomics in Myeloma, Institut Universitaire du Cancer and University Hospital, Centre de Recherche en Cancerologie de Toulouse, Toulouse, France (GRID:grid.468186.5) 
12  Hospital 12 de Octubre, Complentese University, CNIO, CIBERONC, Madrid, Spain (GRID:grid.468186.5) 
13  University of Minho, Braga, Portugal and ICVS/3B’s – PT Government Associate Laboratory, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, Braga/Guimarães, Portugal (GRID:grid.10328.38) (ISNI:0000 0001 2159 175X) 
14  Holy Cross Cancer Center, Department of Hematology, Kielce, Poland (GRID:grid.10328.38); Institute of Hematology and Transfusion Medicine, Department of Hematology, Warsaw, Poland (GRID:grid.419032.d) (ISNI:0000 0001 1339 8589) 
15  University Hospital of Salamanca, CIBERONC, Hematology Department, Salamanca, Spain (GRID:grid.411258.b) 
16  University Hospital of Southern Jutland, Department of Biochemistry, Sønderborg, Denmark (GRID:grid.416811.b) (ISNI:0000 0004 0631 6436); University Hospital of Southern Jutland, IRS-Center Soenderjylland, Aabenraa, Denmark (GRID:grid.416811.b) (ISNI:0000 0004 0631 6436) 
17  Jagiellonian University Medical College, Department of Hematology, Krakow, Poland (GRID:grid.5522.0) (ISNI:0000 0001 2162 9631) 
18  University Hospital No. 2 in Bydgoszcz, Department of Hematology, Bydgoszcz, Poland (GRID:grid.5522.0) 
19  Odense University Hospital, Department of Hematology, Odense, Denmark (GRID:grid.7143.1) (ISNI:0000 0004 0512 5013) 
20  University of Rzeszow, Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, Rzeszow, Poland (GRID:grid.13856.39) (ISNI:0000 0001 2154 3176) 
21  Wroclaw Medical University, Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw, Poland (GRID:grid.4495.c) (ISNI:0000 0001 1090 049X) 
22  Department of Hematology, Rigshospitalet, Copenhagen, Denmark (GRID:grid.475435.4) 
23  Medical University of Lublin, Department of Haemato-oncology and Bone Marrow Transplantation and Department of Internal Medicine in Nursing, Lublin, Poland (GRID:grid.411484.c) (ISNI:0000 0001 1033 7158) 
24  Institute of Hematology and Transfusion Medicine, Department of Hematology, Warsaw, Poland (GRID:grid.419032.d) (ISNI:0000 0001 1339 8589) 
25  University Hospital of Southern Jutland, Department of Biochemistry, Sønderborg, Denmark (GRID:grid.416811.b) (ISNI:0000 0004 0631 6436) 
26  Aarhus University Hospital, Department of Hematology, Aarhus, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X) 
27  Department of Hematology and Transplantology Medical University of Gdansk, Gdańsk, Poland (GRID:grid.11451.30) (ISNI:0000 0001 0531 3426) 
28  Inserm, U900, Institut Curie, PSL University, Paris, France (GRID:grid.4495.c) 
29  U.O. Dipartimento di Ematologia, Azienda USL Toscana Nord Ovest, Livorno, Italy, currently Ospedale Santa Chiara, Pisa, Italy (GRID:grid.144189.1) (ISNI:0000 0004 1756 8209) 
30  University of Minho, Braga, Portugal and ICVS/3B’s – PT Government Associate Laboratory, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, Braga/Guimarães, Portugal (GRID:grid.10328.38) (ISNI:0000 0001 2159 175X); Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil (GRID:grid.427783.d) (ISNI:0000 0004 0615 7498) 
31  Medical University of Lodz, Department of Hematology, Łódź, Poland (GRID:grid.8267.b) (ISNI:0000 0001 2165 3025) 
32  Military Institute of Medicine, Department of Hematology, Warsaw, Poland (GRID:grid.415641.3) (ISNI:0000 0004 0620 0839) 
33  University Hospital in Cracow, Department of Haematology, Cracow, Poland (GRID:grid.412700.0) (ISNI:0000 0001 1216 0093) 
34  Maria Skłodowska-Curie National Research Institute of Oncology, Department of Lymphoid Malignancies, Warsaw, Poland (GRID:grid.418165.f) (ISNI:0000 0004 0540 2543) 
35  Copernicus Memorial Hospital, Laboratory of Clinical and Transplant Immunology and Genetics, Łódź, Poland (GRID:grid.413767.0) 
36  Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Genomic Oncology Area, GENYO, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994); Virgen de las Nieves University Hospital, Hematology Department, Granada, Spain (GRID:grid.411380.f) (ISNI:0000 0000 8771 3783) 
37  German Cancer Research Center (DKFZ), Genomic Epidemiology Group, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
Publication year
2021
Publication date
Apr 2021
Publisher
Springer Nature B.V.
e-ISSN
20445385
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41408-021-00462-y
ProQuest document ID
2512577771
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.