Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival

Background: Leukocyte telomere length has been associated with risk of subsequent pancreatic cancer. Few prospective studies have evaluated the association of prediagnostic leukocyte telomere length with pancreatic cancer survival. Methods: We prospectively examined the association of prediagnostic leukocyte telomere length with overall survival (OS) time among 423 participants diagnosed with pancreatic adenocarcinoma between 1984 and 2008 within the Health Professionals Follow-up Study, Nurses9 Health Study, Physicians9 Health Study, and Women9s Health Initiative. We measured prediagnostic leukocyte telomere length in banked blood samples using quantitative polymerase chain reaction. Cox proportional hazards models were used to estimate hazard ratios (HRs) for OS with adjustment for potential confounders. We also evaluated 10 single nucleotide polymorphisms (SNPs) at the TERT (telomerase reverse transcriptase) locus. Results: Shorter prediagnostic leukocyte telomere length was associated with reduced OS among patients with pancreatic cancer (Ptrend = 0.04). The multivariable-adjusted HR for OS comparing the lowest to highest quintiles of leukocyte telomere length was 1.39 (95% confidence interval, 1.01-1.93), corresponding to a 3-month difference in median OS time. In an analysis excluding cases with blood collected within two years of cancer diagnosis, the association was moderately stronger (HR, 1.55; 95% confidence interval, 1.09-2.21; comparing the lowest to highest quintiles; Ptrend = 0.01). No prognostic association or effect modification for the prognostic association of prediagnostic leukocyte telomere length was noted in relation to the studied SNPs. Conclusions: Prediagnostic leukocyte telomere length was associated with pancreatic cancer survival. Impact: Prediagnostic leukocyte telomere length can be a prognostic biomarker in pancreatic cancer.