TY - JOUR
T1 - Prediagnostic leukocyte telomere length and pancreatic cancer survival
AU - Hamada, Tsuyoshi
AU - Yuan, Chen
AU - Bao, Ying
AU - Zhang, Mingfeng
AU - Khalaf, Natalia
AU - Babic, Ana
AU - Morales-Oyarvide, Vicente
AU - Cochrane, Barbara B.
AU - Michael Gaziano, J.
AU - Giovannucci, Edward L.
AU - Kraft, Peter
AU - Manson, Jo Ann E.
AU - Ng, Kimmie
AU - Nowak, Jonathan A.
AU - Rohan, Thomas E.
AU - Sesso, Howard D.
AU - Stampfer, Meir J.
AU - Amundadottir, Laufey T.
AU - Fuchs, Charles S.
AU - de Vivo, Immaculata
AU - Ogino, Shuji
AU - Wolpin, Brian M.
N1 - Funding Information:
1Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 2Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 5Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 6Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 7University of Washington School of Nursing, Seattle, Washington. 8Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 9Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Jamaica Plain, Massachusetts. 10Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 11Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 12Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and
Funding Information:
The HPFS is supported by U.S. NIH grants UM1 CA167552 and U01 CA167552. The NHS is supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449. The PHS is supported by NIH grants R01 CA097193, R01 CA034944-03, R01 CA040360, R01 HL026490-03, and R01 HL034595-07. The WHI program is supported by the National Heart, Lung, and Blood Institute, NIH, and U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This work was additionally supported by NIH R01 CA205406 and the Broman Fund for Pancreatic Cancer Research to K. Ng; by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), NIH, to L.T. Amundadottir; by NIH R35 CA197735 to S. Ogino; and by Hale Center for Pancreatic Cancer Research, NIH/NCI U01 CA210171, NIH/NCI P50 CA127003, Department of Defense CA130288, Lustgarten Foundation, Pancreatic Cancer Action Network, Stand Up To Cancer, Noble Effort Fund, Peter R. Leavitt Family Fund, Wexler Family Fund, and Promises for Purple to B.M. Wolpin. This research was also supported by a Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research Grant (grant number: SU2C-AACR-DT25-17). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C.
Funding Information:
This research was also supported by a Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer Research Grant (grant number: SU2C-AACR-DT25-17). Stand Up To Cancer is a division
Funding Information:
The HPFS is supported by U.S. NIH grants UM1 CA167552 and U01 CA167552. The NHS is supported by NIH grants UM1 CA186107, P01 CA87969, and R01 CA49449. The PHS is supported by NIH grants R01 CA097193, R01 CA034944-03, R01 CA040360, R01 HL026490-03, and R01
Funding Information:
HL034595-07. The WHI program is supported by the National Heart, Lung, and Blood Institute, NIH, and U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This work was additionally supported by NIH R01 CA205406 and the Broman Fund for Pancreatic Cancer Research to K. Ng; by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), NIH, to L.T. Amundadottir; by NIH R35 CA197735 to S. Ogino; and by Hale Center for Pancreatic Cancer Research, NIH/NCI U01 CA210171, NIH/NCI P50 CA127003, Department of Defense CA130288, Lustgarten Foundation, Pancreatic Cancer Action Network, Stand Up To Cancer, Noble Effort Fund, Peter R. Leavitt Family Fund, Wexler Family Fund, and Promises for Purple to B.M. Wolpin.
Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-19-0577
DO - 10.1158/1055-9965.EPI-19-0577
M3 - Article
C2 - 31427306
AN - SCOPUS:85074445748
VL - 28
SP - 1868
EP - 1875
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 11
ER -