Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Daniele Campa; Alessandro Martino; Judit Varkonyi; Fabienne Lesueur; Krzysztof Jamroziak; Stefano Landi; Artur Jurczyszyn; Herlander Marques; Vibeke Andersen; Manuel Jurado; Hermann Brenner; Mario Petrini; Ulla Vogel; Ramón García-Sanz; Gabriele Buda; Federica Gemignani; Rafael Ríos; Annette Juul Vangsted; Charles Dumontet; Joaquín Martínez-López; María José Moreno; Anna Stępień; Marzena Wątek; Victor Moreno; Aida Karina Dieffenbach; Anna Maria Rossi; Katja Butterbach; Svend E Hove Jacobsen; Hartmut Goldschmidt; Juan Sainz; Jens Hillengass; Enrico Orciuolo; Marek Dudziński; Niels Weinhold; Rui Manuel Reis; Federico Canzian

doi:10.1002/ijc.29101

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Daniele Campa, Alessandro Martino, Judit Varkonyi, Fabienne Lesueur, Krzysztof Jamroziak, Stefano Landi, Artur Jurczyszyn, Herlander Marques, Vibeke Andersen, Manuel Jurado, Hermann Brenner, Mario Petrini, Ulla Vogel, Ramón García-Sanz, Gabriele Buda, Federica Gemignani, Rafael Ríos, Annette Juul Vangsted, Charles Dumontet, Joaquín Martínez-LópezMaría José Moreno, Anna Stępień, Marzena Wątek, Victor Moreno, Aida Karina Dieffenbach, Anna Maria Rossi, Katja Butterbach, Svend E Hove Jacobsen, Hartmut Goldschmidt, Juan Sainz, Jens Hillengass, Enrico Orciuolo, Marek Dudziński, Niels Weinhold, Rui Manuel Reis, Federico Canzian

Institut for Klinisk Medicin

24 Citationer (Scopus)

Abstract

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72-0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63-2.24; p(trend) = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

Originalsprog	Engelsk
Tidsskrift	International Journal of Cancer
Vol/bind	136
Udgave nummer	5
Sider (fra-til)	E351-8
ISSN	0020-7136
DOI	https://doi.org/10.1002/ijc.29101
Status	Udgivet - 1 mar. 2015

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Campa, D., Martino, A., Varkonyi, J., Lesueur, F., Jamroziak, K., Landi, S., Jurczyszyn, A., Marques, H., Andersen, V., Jurado, M., Brenner, H., Petrini, M., Vogel, U., García-Sanz, R., Buda, G., Gemignani, F., Ríos, R., Vangsted, A. J., Dumontet, C., ... Canzian, F. (2015). Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length. International Journal of Cancer, 136(5), E351-8. https://doi.org/10.1002/ijc.29101

Campa, D, Martino, A, Varkonyi, J, Lesueur, F, Jamroziak, K, Landi, S, Jurczyszyn, A, Marques, H, Andersen, V, Jurado, M, Brenner, H, Petrini, M, Vogel, U, García-Sanz, R, Buda, G, Gemignani, F, Ríos, R, Vangsted, AJ, Dumontet, C, Martínez-López, J, Moreno, MJ, Stępień, A, Wątek, M, Moreno, V, Dieffenbach, AK, Rossi, AM, Butterbach, K, Jacobsen, SEH, Goldschmidt, H, Sainz, J, Hillengass, J, Orciuolo, E, Dudziński, M, Weinhold, N, Reis, RM & Canzian, F 2015, 'Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length', International Journal of Cancer, bind 136, nr. 5, s. E351-8. https://doi.org/10.1002/ijc.29101

@article{b18c217a8d9943efa99397232319219b,

title = "Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length",

abstract = "Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72-0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63-2.24; p(trend) = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.",

keywords = "Aged, Case-Control Studies, Cohort Studies, Computational Biology, Female, Follow-Up Studies, Genetic Predisposition to Disease, Germany, Humans, Leukocytes, Male, Middle Aged, Multiple Myeloma, Polymorphism, Genetic, Prognosis, Risk Factors, Telomerase, Telomere Homeostasis",

author = "Daniele Campa and Alessandro Martino and Judit Varkonyi and Fabienne Lesueur and Krzysztof Jamroziak and Stefano Landi and Artur Jurczyszyn and Herlander Marques and Vibeke Andersen and Manuel Jurado and Hermann Brenner and Mario Petrini and Ulla Vogel and Ram{\'o}n Garc{\'i}a-Sanz and Gabriele Buda and Federica Gemignani and Rafael R{\'i}os and Vangsted, {Annette Juul} and Charles Dumontet and Joaqu{\'i}n Mart{\'i}nez-L{\'o}pez and Moreno, {Mar{\'i}a Jos{\'e}} and Anna St{\c e}pie{\'n} and Marzena W{\c a}tek and Victor Moreno and Dieffenbach, {Aida Karina} and Rossi, {Anna Maria} and Katja Butterbach and Jacobsen, {Svend E Hove} and Hartmut Goldschmidt and Juan Sainz and Jens Hillengass and Enrico Orciuolo and Marek Dudzi{\'n}ski and Niels Weinhold and Reis, {Rui Manuel} and Federico Canzian",

note = "{\textcopyright} 2014 UICC.",

year = "2015",

month = mar,

day = "1",

doi = "10.1002/ijc.29101",

language = "English",

volume = "136",

pages = "E351--8",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

number = "5",

}

TY - JOUR

T1 - Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

AU - Campa, Daniele

AU - Martino, Alessandro

AU - Varkonyi, Judit

AU - Lesueur, Fabienne

AU - Jamroziak, Krzysztof

AU - Landi, Stefano

AU - Jurczyszyn, Artur

AU - Marques, Herlander

AU - Andersen, Vibeke

AU - Jurado, Manuel

AU - Brenner, Hermann

AU - Petrini, Mario

AU - Vogel, Ulla

AU - García-Sanz, Ramón

AU - Buda, Gabriele

AU - Gemignani, Federica

AU - Ríos, Rafael

AU - Vangsted, Annette Juul

AU - Dumontet, Charles

AU - Martínez-López, Joaquín

AU - Moreno, María José

AU - Stępień, Anna

AU - Wątek, Marzena

AU - Moreno, Victor

AU - Dieffenbach, Aida Karina

AU - Rossi, Anna Maria

AU - Butterbach, Katja

AU - Jacobsen, Svend E Hove

AU - Goldschmidt, Hartmut

AU - Sainz, Juan

AU - Hillengass, Jens

AU - Orciuolo, Enrico

AU - Dudziński, Marek

AU - Weinhold, Niels

AU - Reis, Rui Manuel

AU - Canzian, Federico

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72-0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63-2.24; p(trend) = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

AB - Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72-0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy-free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63-2.24; p(trend) = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

KW - Aged

KW - Case-Control Studies

KW - Cohort Studies

KW - Computational Biology

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Germany

KW - Humans

KW - Leukocytes

KW - Male

KW - Middle Aged

KW - Multiple Myeloma

KW - Polymorphism, Genetic

KW - Prognosis

KW - Risk Factors

KW - Telomerase

KW - Telomere Homeostasis

U2 - 10.1002/ijc.29101

DO - 10.1002/ijc.29101

M3 - Journal article

C2 - 25066524

SN - 0020-7136

VL - 136

SP - E351-8

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 5

ER -

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

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