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Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival.

ABSTRACT: 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, Nurses' Health Study, Physicians' Health Study, and Women's Health Initiative. We measured prediagnostic leukocyte telomere length in banked blood samples using quantitative PCR. Cox proportional hazards models were used to estimate HRs for OS with adjustment for potential confounders. We also evaluated 10 SNPs at the telomerase reverse transcriptase locus. RESULTS:Shorter prediagnostic leukocyte telomere length was associated with reduced OS among patients with pancreatic cancer (P trend = 0.04). The multivariable-adjusted HR for OS comparing the lowest with 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 2 years of cancer diagnosis, the association was moderately stronger (HR, 1.55; 95% confidence interval, 1.09-2.21; comparing the lowest with highest quintiles; P trend = 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.

SUBMITTER: Hamada T

PROVIDER: S-EPMC6825575 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival.

Hamada Tsuyoshi T Yuan Chen C Bao Ying Y Zhang Mingfeng M Khalaf Natalia N Babic Ana A Morales-Oyarvide Vicente V Cochrane Barbara B BB Gaziano J Michael JM Giovannucci Edward L EL Kraft Peter P Manson JoAnn E JE Ng Kimmie K Nowak Jonathan A JA Rohan Thomas E TE Sesso Howard D HD Stampfer Meir J MJ Amundadottir Laufey T LT Fuchs Charles S CS De Vivo Immaculata I Ogino Shuji S Wolpin Brian M BM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20190819 11

<h4>Background</h4>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.<h4>Methods</h4>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 S ...[more]

PMID: 31427306

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Project description:IntroductionTelomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study.MethodsThe Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors.ResultsLonger telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25-3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17-8.11) for adenocarcinoma patients and 1.47 (0.43-5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22-5.13) and 1.63 (0.66-4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk.ConclusionsThe present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer.

Dataset Information

Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival.

Publications

Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival.

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