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. 2021 Apr 14;11(4):74.
doi: 10.1038/s41408-021-00462-y.

Genetically determined telomere length and multiple myeloma risk and outcome

Matteo Giaccherini  1 , Angelica Macauda  1   2 , Enrico Orciuolo  3 , Marcin Rymko  4 , Karolina Gruenpeter  5 , Charles Dumontet  6 , Malgorzata Raźny  7 , Victor Moreno  8 , Gabriele Buda  3 , Katia Beider  9 , Judit Varkonyi  10 , Hervé Avet-Loiseau  11 , Joaquín Martinez-Lopez  12 , Herlander Marques  13 , Marzena Watek  14   15 , Maria Eugenia Sarasquete  16 , Vibeke Andersen  17   18 , Lionel Karlin  6 , Anna Suska  19 , Marcin Kruszewski  20 , Niels Abildgaard  21 , Marek Dudziński  22 , Aleksandra Butrym  23 , Arnold Nagler  9 , Annette Juul Vangsted  24 , Katalin Kadar  10 , Tomczak Waldemar  25 , Krzysztof Jamroziak  15 , Svend Erik Hove Jacobsen  17 , Lene Hyldahl Ebbesen  26 , Michał Taszner  27 , Grzegorz Mazur  23 , Fabienne Lesueur  28 , Matteo Pelosini  29 , Ramon Garcia-Sanz  16 , Artur Jurczyszyn  19 , Delphine Demangel  6 , Rui Manuel Reis  13   30 , Elżbieta Iskierka-Jażdżewska  31 , Miroslaw Markiewicz  22 , Federica Gemignani  1 , Edyta Subocz  32 , Daria Zawirska  33 , Agnieszka Druzd-Sitek  34 , Anna Stępień  35 , M Henar Alonso  8 , Juan Sainz  36   37 , Federico Canzian #  38 , Daniele Campa #  1
Affiliations

Genetically determined telomere length and multiple myeloma risk and outcome

Matteo Giaccherini et al. Blood Cancer J. .

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.

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