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; ptrend = 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.

Prognostic relevance of telomere length and telomerase reverse transcriptase variant (rs2242652) on the multiple myeloma patients

“…Our finding disagrees with Campa et al that reported the association of the minor allele of rs2242652 with decreased risk of MM. Zhang et al found that TERT rs2242652 served as protective factors for the formation of hepatocellular carcinoma, which may be due to the reduced expression of TERT protein by this SNP.…”

“…In the present study, there was no significant association of rs2242652 with relative telomere length. This observation was in agreement with Campa et al However, Bojesen et al result that this polymorphism was strongly associated with telomere length.…”

“…The main interesting finding in our study was that the telomeres were significantly longer in MM patients as compared to controls in spite the fact of short telomere with age. This finding was in agreement with that reported by Campa et al who measured the leukocyte telomere length (LTL) in a group of 140 newly diagnosed MM cases and 468 controls; this finding could be explained on the basis of hypothesis by Jones et al, who concluded that longer telomeres might be a marker of an actively reproducing cell that has an increased chance of acquiring tumor as the telomerase reactivation and telomerase‐mediated elongation of shorter telomeres is a feature of multiple myeloma and TERT inhibition could be serve as a therapeutic strategy approach in future of those MM patients.…”

Identification of miRSNPs associated with the risk of multiple myeloma

“…2 Several risk loci have been proposed and a few have been identified through candidate gene and genome-wide association studies (GWAS). [3][4][5][6][7][8][9][10] Some of these loci are involved in complex pathways related to cell cycle, cell proliferation and DNA repair, in which micro-RNAs (miRNAs) have a proven regulatory role. 11 MiRNAs are small non-coding RNA molecules, 20-25 nucleotides long, highly conserved throughout evolution.…”

“…Converging evidence of MM in monozygotic twins and familial aggregation of MM strongly suggest that MM aetiology has a robust genetic component as well . Several risk loci have been proposed and a few have been identified through candidate gene and genome‐wide association studies (GWAS) . Some of these loci are involved in complex pathways related to cell cycle, cell proliferation and DNA repair, in which micro‐RNAs (miRNAs) have a proven regulatory role …”