Prediagnostic leukocyte telomere length and pancreatic cancer survival

Tsuyoshi Hamada, Chen Yuan, Ying Bao, Mingfeng Zhang, Natalia Khalaf, Ana Babic, Vicente Morales-Oyarvide, Barbara B. Cochrane, J. Michael Gaziano, Edward L. Giovannucci, Peter Kraft, Jo Ann E. Manson, Kimmie Ng, Jonathan A. Nowak, Thomas E. Rohan, Howard D. Sesso, Meir J. Stampfer, Laufey T. Amundadottir, Charles S. Fuchs, Immaculata de VivoShuji Ogino, Brian M. Wolpin

Research output: Contribution to journalArticle

5 Scopus citations

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 (Ptrend ¼ 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; Ptrend ¼ 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.

Original languageEnglish (US)
Pages (from-to)1868-1875
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number11
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Hamada, T., Yuan, C., Bao, Y., Zhang, M., Khalaf, N., Babic, A., Morales-Oyarvide, V., Cochrane, B. B., Michael Gaziano, J., Giovannucci, E. L., Kraft, P., Manson, J. A. E., Ng, K., Nowak, J. A., Rohan, T. E., Sesso, H. D., Stampfer, M. J., Amundadottir, L. T., Fuchs, C. S., ... Wolpin, B. M. (2019). Prediagnostic leukocyte telomere length and pancreatic cancer survival. Cancer Epidemiology Biomarkers and Prevention, 28(11), 1868-1875. https://doi.org/10.1158/1055-9965.EPI-19-0577