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    Keywords: DISEASE ; BREAST ; COMMON VARIANT ; PULMONARY-FIBROSIS ; GENOME-WIDE ASSOCIATION ; TERT ; CANCER SUSCEPTIBILITY LOCI ; 5P15.33 ; IMMEnSE consortium ; 6P21.33
    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. What's new? A critical element of cancer cell immortality is the maintenance of telomere length, a process that is influenced in part by genetic variations in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). At the TERT locus in particular, certain variations are linked with either increased or decreased risk of a variety of malignancies. In the present study, a variant of TERT known as rs2242652 was associated with reduced risk of multiple myeloma. Compared with controls, patients with multiple myeloma were found to possess longer telomeres, suggesting an association between increased telomere length and increased multiple myeloma risk.
    Type of Publication: Journal article published
    PubMed ID: 25066524
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