Shorter Treatment-Naïve Leukocyte Telomere Length is Associated with Poorer Overall Survival of Patients with Pancreatic Ductal Adenocarcinoma

Background: Critically shortened telomeres contribute to chromosomal instability and neoplastic transformation and are associated with early death of patients with certain cancer types. Shorter leukocyte telomere length (LTL) has been associated with higher risk for pancreatic ductal adenocarcinoma (PDAC) and might be associated also with survival of patients with PDAC. We investigated the association between treatment-naïve LTL and overall survival of patients with incident PDAC.

Methods: The study included 642 consecutively enrolled PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreas Research. Blood samples were obtained at the time of diagnosis, before the start of cancer treatment, from which LTL was assayed by qRT-PCR. LTL was first modeled as a continuous variable (per-interquartile range decrease in LTL) and then as a categorized variable (short, medium, long). Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated for overall mortality using Cox proportional hazard models.

Results: Shorter treatment-naïve LTL was associated with higher mortality among patients with PDAC (HR_continuous = 1.13, 95% CI: 1.01–1.28, P = 0.03; HR_{shortest vs. longest LTL} = 1.29, 95% CI: 1.05–1.59, P_trend = 0.01). There was a difference in the association between LTL and overall mortality by tumor stage at diagnosis; resectable tumors (HR_continuous = 0.91; 95% CI: 0.73–1.12), locally advanced tumors (HR_continuous = 1.29; 95% CI: 1.07–1.56), and metastatic tumors (HR_continuous = 1.17; 95% CI: 0.96–1.42), P_interaction = 0.04.

Conclusion: Shorter treatment-naïve LTL is associated with poorer overall survival of patients with incident PDAC.

Impact: Peripheral blood LTL might be a prognostic marker for PDAC.