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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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Research Articles

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, JoAnn E. Manson, Kimmie Ng, Jonathan A. Nowak, Thomas E. Rohan, Howard D. Sesso, Meir J. Stampfer, Laufey T. Amundadottir, Charles S. Fuchs, Immaculata De Vivo, Shuji Ogino and Brian M. Wolpin
Tsuyoshi Hamada
Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
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  • For correspondence: hamada-tky@umin.ac.jp
Chen Yuan
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Ying Bao
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Mingfeng Zhang
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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Natalia Khalaf
Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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  • ORCID record for Natalia Khalaf
Ana Babic
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
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Vicente Morales-Oyarvide
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
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Barbara B. Cochrane
University of Washington School of Nursing, Seattle, Washington.
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  • ORCID record for Barbara B. Cochrane
J. Michael Gaziano
Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Jamaica Plain, Massachusetts.
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Edward L. Giovannucci
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Peter Kraft
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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JoAnn E. Manson
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Kimmie Ng
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
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Jonathan A. Nowak
Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Thomas E. Rohan
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
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Howard D. Sesso
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Meir J. Stampfer
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Laufey T. Amundadottir
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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Charles S. Fuchs
Yale Cancer Center, New Haven, Connecticut.Department of Medicine, Yale School of Medicine, New Haven, Connecticut.Smilow Cancer Hospital, New Haven, Connecticut.
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Immaculata De Vivo
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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Shuji Ogino
Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.
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Brian M. Wolpin
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
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DOI: 10.1158/1055-9965.EPI-19-0577 Published November 2019
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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 = 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 = 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.

This article is featured in Highlights of This Issue, p. 1769

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Cancer Epidemiol Biomarkers Prev 2019;28:1868–75

  • Received May 19, 2019.
  • Revision received July 12, 2019.
  • Accepted August 13, 2019.
  • Published first August 19, 2019.
  • ©2019 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 28 (11)
November 2019
Volume 28, Issue 11
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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, JoAnn E. Manson, Kimmie Ng, Jonathan A. Nowak, Thomas E. Rohan, Howard D. Sesso, Meir J. Stampfer, Laufey T. Amundadottir, Charles S. Fuchs, Immaculata De Vivo, Shuji Ogino and Brian M. Wolpin
Cancer Epidemiol Biomarkers Prev November 1 2019 (28) (11) 1868-1875; DOI: 10.1158/1055-9965.EPI-19-0577

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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, JoAnn E. Manson, Kimmie Ng, Jonathan A. Nowak, Thomas E. Rohan, Howard D. Sesso, Meir J. Stampfer, Laufey T. Amundadottir, Charles S. Fuchs, Immaculata De Vivo, Shuji Ogino and Brian M. Wolpin
Cancer Epidemiol Biomarkers Prev November 1 2019 (28) (11) 1868-1875; DOI: 10.1158/1055-9965.EPI-19-0577
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