Genetically determined telomere length and multiple myeloma risk and outcome

Matteo Giaccherini¹, Angelica Macauda^{1

2}, Enrico Orciuolo³, Marcin Rymko⁴, Karolina Gruenpeter⁵, Charles Dumontet⁶, Malgorzata Raźny⁷, Victor Moreno⁸, Gabriele Buda³, Katia Beider⁹, Judit Varkonyi¹⁰, Hervé Avet-Loiseau¹¹, Joaquín Martinez-Lopez¹², Herlander Marques¹³, Marzena Watek^{14

15}, Maria Eugenia Sarasquete¹⁶, Vibeke Andersen^{17

18}, Lionel Karlin⁶, Anna Suska¹⁹, Marcin Kruszewski²⁰, Niels Abildgaard²¹, Marek Dudziński²², Aleksandra Butrym²³, Arnold Nagler⁹, Annette Juul Vangsted²⁴, Katalin Kadar¹⁰, Tomczak Waldemar²⁵, Krzysztof Jamroziak¹⁵, Svend Erik Hove Jacobsen¹⁷, Lene Hyldahl Ebbesen²⁶, Michał Taszner²⁷, Grzegorz Mazur²³, Fabienne Lesueur²⁸, Matteo Pelosini²⁹, Ramon Garcia-Sanz¹⁶, Artur Jurczyszyn¹⁹, Delphine Demangel⁶, Rui Manuel Reis^{13

30}, Elżbieta Iskierka-Jażdżewska³¹, Miroslaw Markiewicz²², Federica Gemignani¹, Edyta Subocz³², Daria Zawirska³³, Agnieszka Druzd-Sitek³⁴, Anna Stępień³⁵, M Henar Alonso⁸, Juan Sainz^{36

37}, Federico Canzian^#³⁸, Daniele Campa^#¹

Affiliations

¹ Department of Biology, University of Pisa, Pisa, Italy.
² Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴ Department of Hematology, Copernicus Hospital, Torun, Poland.
⁵ Department of Haematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
⁶ Hospices Civils de Lyon, Lyon, France.
⁷ Department of Hematology, Rydygier Specialistic Hospital, Cracow, Poland.
⁸ Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
⁹ Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
¹⁰ Semmelweis University, Budapest, Hungary.
¹¹ Laboratory for Genomics in Myeloma, Institut Universitaire du Cancer and University Hospital, Centre de Recherche en Cancerologie de Toulouse, Toulouse, France.
¹² Hospital 12 de Octubre, Complentese University, CNIO, CIBERONC, Madrid, Spain.
¹³ Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
¹⁴ Department of Hematology, Holy Cross Cancer Center, Kielce, Poland.
¹⁵ Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
¹⁶ Hematology Department, University Hospital of Salamanca, CIBERONC, Salamanca, Spain.
¹⁷ Department of Biochemistry, University Hospital of Southern Jutland, Sønderborg, Denmark.
¹⁸ IRS-Center Soenderjylland, University Hospital of Southern Jutland, Aabenraa, Denmark.
¹⁹ Department of Hematology, Jagiellonian University Medical College, Krakow, Poland.
²⁰ Department of Hematology, University Hospital No. 2 in Bydgoszcz, Bydgoszcz, Poland.
²¹ Department of Hematology, Odense University Hospital, Odense, Denmark.
²² Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, Poland.
²³ Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland.
²⁴ Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
²⁵ Department of Haemato-oncology and Bone Marrow Transplantation and Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland.
²⁶ Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
²⁷ Department of Hematology and Transplantology Medical University of Gdansk, Gdańsk, Poland.
²⁸ Inserm, U900, Institut Curie, PSL University, Mines ParisTech, Paris, France.
²⁹ U.O. Dipartimento di Ematologia, Azienda USL Toscana Nord Ovest, Livorno, Italy, currently Ospedale Santa Chiara, Pisa, Italy.
³⁰ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
³¹ Department of Hematology, Medical University of Lodz, Łódź, Poland.
³² Department of Hematology, Military Institute of Medicine, Warsaw, Poland.
³³ Department of Haematology, University Hospital in Cracow, Cracow, Poland.
³⁴ Department of Lymphoid Malignancies, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
³⁵ Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Łódź, Poland.
³⁶ Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
³⁷ Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
³⁸ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. f.canzian@dkfz.de.

^# Contributed equally.

PMID: 33854038
PMCID: PMC8046773
DOI: 10.1038/s41408-021-00462-y

Genetically determined telomere length and multiple myeloma risk and outcome

Matteo Giaccherini et al. Blood Cancer J. 2021.

. 2021 Apr 14;11(4):74.

doi: 10.1038/s41408-021-00462-y.

Authors

Affiliations

¹ Department of Biology, University of Pisa, Pisa, Italy.
² Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³ Haematology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁴ Department of Hematology, Copernicus Hospital, Torun, Poland.
⁵ Department of Haematology and Bone Marrow Transplantation, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
⁶ Hospices Civils de Lyon, Lyon, France.
⁷ Department of Hematology, Rydygier Specialistic Hospital, Cracow, Poland.
⁸ Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), IDIBELL, CIBERESP and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
⁹ Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.
¹⁰ Semmelweis University, Budapest, Hungary.
¹¹ Laboratory for Genomics in Myeloma, Institut Universitaire du Cancer and University Hospital, Centre de Recherche en Cancerologie de Toulouse, Toulouse, France.
¹² Hospital 12 de Octubre, Complentese University, CNIO, CIBERONC, Madrid, Spain.
¹³ Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
¹⁴ Department of Hematology, Holy Cross Cancer Center, Kielce, Poland.
¹⁵ Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
¹⁶ Hematology Department, University Hospital of Salamanca, CIBERONC, Salamanca, Spain.
¹⁷ Department of Biochemistry, University Hospital of Southern Jutland, Sønderborg, Denmark.
¹⁸ IRS-Center Soenderjylland, University Hospital of Southern Jutland, Aabenraa, Denmark.
¹⁹ Department of Hematology, Jagiellonian University Medical College, Krakow, Poland.
²⁰ Department of Hematology, University Hospital No. 2 in Bydgoszcz, Bydgoszcz, Poland.
²¹ Department of Hematology, Odense University Hospital, Odense, Denmark.
²² Department of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, Rzeszow, Poland.
²³ Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland.
²⁴ Department of Hematology, Rigshospitalet, Copenhagen, Denmark.
²⁵ Department of Haemato-oncology and Bone Marrow Transplantation and Department of Internal Medicine in Nursing, Medical University of Lublin, Lublin, Poland.
²⁶ Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
²⁷ Department of Hematology and Transplantology Medical University of Gdansk, Gdańsk, Poland.
²⁸ Inserm, U900, Institut Curie, PSL University, Mines ParisTech, Paris, France.
²⁹ U.O. Dipartimento di Ematologia, Azienda USL Toscana Nord Ovest, Livorno, Italy, currently Ospedale Santa Chiara, Pisa, Italy.
³⁰ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
³¹ Department of Hematology, Medical University of Lodz, Łódź, Poland.
³² Department of Hematology, Military Institute of Medicine, Warsaw, Poland.
³³ Department of Haematology, University Hospital in Cracow, Cracow, Poland.
³⁴ Department of Lymphoid Malignancies, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
³⁵ Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Łódź, Poland.
³⁶ Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
³⁷ Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain.
³⁸ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. f.canzian@dkfz.de.

^# Contributed equally.

PMID: 33854038
PMCID: PMC8046773
DOI: 10.1038/s41408-021-00462-y

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.

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Conflict of interest statement

The authors declare no competing interests.

References

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Genetically determined telomere length and multiple myeloma risk and outcome

Affiliations

Genetically determined telomere length and multiple myeloma risk and outcome

Authors

Affiliations

Abstract

Conflict of interest statement

References

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Full Text Sources

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Medical