Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival

被引:16
|
作者
Hamada, Tsuyoshi [1 ,2 ]
Yuan, Chen [2 ,3 ,4 ]
Bao, Ying [2 ,5 ]
Zhang, Mingfeng [6 ]
Khalaf, Natalia [2 ,7 ]
Babic, Ana [2 ,3 ]
Morales-Oyarvide, Vicente [2 ,3 ]
Cochrane, Barbara B. [8 ]
Gaziano, J. Michael [2 ,9 ,10 ]
Giovannucci, Edward L. [2 ,4 ,5 ,11 ]
Kraft, Peter [4 ,12 ]
Manson, JoAnn E. [2 ,4 ,5 ,9 ]
Ng, Kimmie [2 ,3 ]
Nowak, Jonathan A. [2 ,13 ]
Rohan, Thomas E. [14 ]
Sesso, Howard D. [2 ,4 ,9 ]
Stampfer, Meir J. [2 ,4 ,5 ,11 ]
Amundadottir, Laufey T. [6 ]
Fuchs, Charles S. [15 ,16 ,17 ]
De Vivo, Immaculata [2 ,4 ,5 ]
Ogino, Shuji [1 ,2 ,4 ,13 ,18 ]
Wolpin, Brian M. [2 ,3 ]
机构
[1] Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02115 USA
[2] Harvard Med Sch, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[4] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
[5] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA
[6] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA
[7] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA
[8] Univ Washington, Sch Nursing, Seattle, WA 98195 USA
[9] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA
[10] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Jamaica Plain, MA USA
[11] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA
[12] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA
[13] Brigham & Womens Hosp, Dept Pathol, Program MPE Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA
[14] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA
[15] Yale Canc Ctr, New Haven, CT USA
[16] Yale Sch Med, Dept Med, New Haven, CT USA
[17] Smilow Canc Hosp, New Haven, CT USA
[18] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
关键词
GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; RISK; MORTALITY; HEALTH; METAANALYSIS; PROGNOSIS; DISEASE; OVARIAN; INDEX;
D O I
10.1158/1055-9965.EPI-19-0577
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:1868 / 1875
页数:8
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