Prognostic role of telomere length in malignancies: A meta-analysis and meta-regression

Abstract

Telomere length (TL) has been associated with several health conditions including cancer. To quantify the effect of TL on outcomes in malignancies and explore the role of type of TL measurement we conducted a librarian-led systematic search of electronic databases identified publications exploring the prognostic role of TL on cancer outcomes. Overall survival (OS) was the primary outcome measure while other time-to-event endpoints were secondary outcomes. Data from studies reporting a hazard ratio (HR) with 95% confidence interval (CI) and/or p-value were pooled in a meta-analysis. HRs were weighted by generic inverse variance and computed by random effects modeling. All statistical tests were two-sided. Sixty-one studies comprising a total of 14,720 patients were included of which 41 (67%) reported OS outcomes. Overall, the pooled HR for OS was 0.88 (95%CI=0.69-1.11, p=0.28). Long (versus short) telomeres were associated with improved outcomes in chronic lymphatic leukemia (CLL) and urothelial cancer (HR=0.45, 95%CI=0.29-0.71 and HR=0.68, 95%CI=0.46-1.00, respectively), conversely worse OS was seen with hepatocellular carcinoma (HR=1.90, 95%CI=1.51-2.38). Pooled HRs (95% CI) for progression-free survival, relapse/disease-free survival, cancer-specific survival, and treatment-free survival were 0.56 (0.41-0.76), 0.76 (0.53-1.10), 0.72 (0.48-1.10), and 0.48 (0.39-0.60), respectively. There was substantial heterogeneity of tissues and methods used for TL measurement and no clear association between TL and outcome was identified in subgroups. In conclusion, there is inconsistent effect of TL on cancer outcomes possibly due to variable methods of measurement. Standardization of measurement and reporting of TL is warranted before the prognostic value of TL can be accurately assessed.

Keywords: Cancer; Malignancy; Meta-analysis; Meta-regression; Prognosis; Telomere length.