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Genetically determined telomere length and multiple myeloma risk and outcome
- Source :
- Giaccherini, M, Macauda, A, Orciuolo, E, Rymko, M, Gruenpeter, K, Dumontet, C, Raźny, M, Moreno, V, Buda, G, Beider, K, Varkonyi, J, Avet-Loiseau, H, Martinez-Lopez, J, Marques, H, Watek, M, Sarasquete, M E, Andersen, V, Karlin, L, Suska, A, Kruszewski, M, Abildgaard, N, Dudziński, M, Butrym, A, Nagler, A, Vangsted, A J, Kadar, K, Waldemar, T, Jamroziak, K, Jacobsen, S E H, Ebbesen, L H, Taszner, M, Mazur, G, Lesueur, F, Pelosini, M, Garcia-Sanz, R, Jurczyszyn, A, Demangel, D, Reis, R M, Iskierka-Jażdżewska, E, Markiewicz, M, Gemignani, F, Subocz, E, Zawirska, D, Druzd-Sitek, A, Stępień, A, Alonso, M H, Sainz, J, Canzian, F & Campa, D 2021, ' Genetically determined telomere length and multiple myeloma risk and outcome ', Blood Cancer Journal, vol. 11, no. 4, 74 . https://doi.org/10.1038/s41408-021-00462-y, Blood Cancer Journal, Vol 11, Iss 4, Pp 1-10 (2021), Dipòsit Digital de la UB, Universidad de Barcelona, Blood Cancer Journal, Digibug. Repositorio Institucional de la Universidad de Granada, instname, Digibug: Repositorio Institucional de la Universidad de Granada, Universidad de Granada (UGR)
- Publication Year :
- 2021
-
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.<br />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.<br />Univerity of Pisa<br />Helmholtz Association<br />Instituto de Salud Carlos III PI12/02688 PI17/02276<br />Instituto de Salud Carlos III<br />European Commission<br />FEDER funds-a way to build Europe PI14-00613<br />Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) 2017SGR723<br />Projekt DEAL
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Giaccherini, M, Macauda, A, Orciuolo, E, Rymko, M, Gruenpeter, K, Dumontet, C, Raźny, M, Moreno, V, Buda, G, Beider, K, Varkonyi, J, Avet-Loiseau, H, Martinez-Lopez, J, Marques, H, Watek, M, Sarasquete, M E, Andersen, V, Karlin, L, Suska, A, Kruszewski, M, Abildgaard, N, Dudziński, M, Butrym, A, Nagler, A, Vangsted, A J, Kadar, K, Waldemar, T, Jamroziak, K, Jacobsen, S E H, Ebbesen, L H, Taszner, M, Mazur, G, Lesueur, F, Pelosini, M, Garcia-Sanz, R, Jurczyszyn, A, Demangel, D, Reis, R M, Iskierka-Jażdżewska, E, Markiewicz, M, Gemignani, F, Subocz, E, Zawirska, D, Druzd-Sitek, A, Stępień, A, Alonso, M H, Sainz, J, Canzian, F & Campa, D 2021, ' Genetically determined telomere length and multiple myeloma risk and outcome ', Blood Cancer Journal, vol. 11, no. 4, 74 . https://doi.org/10.1038/s41408-021-00462-y, Blood Cancer Journal, Vol 11, Iss 4, Pp 1-10 (2021), Dipòsit Digital de la UB, Universidad de Barcelona, Blood Cancer Journal, Digibug. Repositorio Institucional de la Universidad de Granada, instname, Digibug: Repositorio Institucional de la Universidad de Granada, Universidad de Granada (UGR)
- Accession number :
- edsair.doi.dedup.....d0595cb0b8571fdb63b067a3612189c4