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.
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Daniele
authors: D
authors: Campa
authors: Alessandro
authors: A
authors: Martino
authors: Judit
authors: J
authors: Varkonyi
authors: Fabienne
authors: F
authors: Lesueur
authors: Krzysztof
authors: K
authors: Jamroziak
authors: Stefano
authors: S
authors: Landi
authors: Artur
authors: A
authors: Jurczyszyn
authors: Herlander
authors: H
authors: Marques
authors: Vibeke
authors: V
authors: Andersen
authors: Manuel
authors: M
authors: Jurado
authors: Hermann
authors: H
authors: Brenner
authors: Mario
authors: M
authors: Petrini
authors: Ulla
authors: U
authors: Vogel
authors: Ramón
authors: R
authors: García-Sanz
authors: Gabriele
authors: G
authors: Buda
authors: Federica
authors: F
authors: Gemignani
authors: Rafael
authors: R
authors: Ríos
authors: Annette Juul
authors: AJ
authors: Vangsted
authors: Charles
authors: C
authors: Dumontet
authors: Joaquín
authors: J
authors: Martínez-López
authors: María José
authors: MJ
authors: Moreno
authors: Anna
authors: A
authors: Stępień
authors: Marzena
authors: M
authors: Wątek
authors: Victor
authors: V
authors: Moreno
authors: Aida Karina
authors: AK
authors: Dieffenbach
authors: Anna Maria
authors: AM
authors: Rossi
authors: Katja
authors: K
authors: Butterbach
authors: Svend E Hove
authors: SE
authors: Jacobsen
authors: Hartmut
authors: H
authors: Goldschmidt
authors: Juan
authors: J
authors: Sainz
authors: Jens
authors: J
authors: Hillengass
authors: Enrico
authors: E
authors: Orciuolo
authors: Marek
authors: M
authors: Dudziński
authors: Niels
authors: N
authors: Weinhold
authors: Rui Manuel
authors: RM
authors: Reis
authors: Federico
authors: F
authors: Canzian
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: multiple myeloma; polymorphisms; susceptibility; telomerase; telomere length