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: 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
• Journal: International journal of cancer (Int J Cancer) Vol. 136 Issue 5 Pg. E351-8 (Mar 01 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25066524 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• TERT protein, human
• Telomerase

Topics

• Aged
• Case-Control Studies
• Cohort Studies
• Computational Biology
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Germany (epidemiology)
• Humans
• Leukocytes
• Male
• Middle Aged
• Multiple Myeloma (epidemiology, genetics)
• Polymorphism, Genetic (genetics)
• Prognosis
• Risk Factors
• Telomerase (genetics)
• Telomere Homeostasis (genetics)