Abstract
Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the “teloscore” in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36–2.11; P = 2.97 × 10−6 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86–0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.
Highlights
Multiple myeloma (MM) is a plasma cell malignancy that arises from a single clone of malignant plasma cells (PCs) in the bone marrow
MM was not among the tumors investigated by the authors and the only study conducted on MM survival consisted of five patients where telomere length was measured in bone marrow cells, comparing malignant vs. non-malignant cells[28]
All the selected single nucleotide polymorphisms (SNPs) were in Hardy–Weinberg Equilibrium (HWE) in the control population
Summary
Multiple myeloma (MM) is a plasma cell malignancy that arises from a single clone of malignant plasma cells (PCs) in the bone marrow. It has a worldwide incidence of 2.1/100,000 new cases every year, ranking as the second. In the recent years the importance of genetics has emerged in MM response to treatment and survival[9,10,11,12,13,14,15] Alongside polymorphic variants, another emerging marker of susceptibility and prognosis for several diseases is telomere length. MM was not among the tumors investigated by the authors and the only study conducted on MM survival consisted of five patients where telomere length was measured in bone marrow cells, comparing malignant vs. non-malignant cells[28]
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