title: Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the United States.
abstract: BACKGROUND
  Telomere shortening is an important molecular event in hepatocellular carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is less clear. Our study aimed to examine the association of telomere length with survival of patients with HCC.
  
  
  METHODS
  We measured telomere length in tumor and adjacent non-tumor tissues from 126 persons with HCC in the United States (U.S.) who were followed for mortality outcomes. Relative telomere length (RTL) was measured by a monochrome multiplex quantitative polymerase chain reaction assay. Multivariable Cox proportional hazards modeling was used to calculate hazard ratios (HRs) and 95% CIs for the association between telomere length and all-cause mortality. We also examined associations between telomere length and patient characteristics using multiple linear regression.
  
  
  RESULTS
  During a mean follow-up of 6.0 years, 79 deaths occurred among 114 individuals for whom survival data were available. The ratio of RTL in tumor relative to non-tumor tissue was greater for individuals with regional or distant stage tumors (0.97) than localized stage tumors (0.77), and for individuals with grade III or IV tumors (0.95) than grade II (0.88) or grade I (0.67) tumors. An RTL ratio ≥1 was not associated with survival (HR 0.92, 95% CI 0.55, 1.55) compared to a ratio <1, after adjusting for age at diagnosis, sex, tumor stage and tumor size. Similarly, RTL in the tumor and non-tumor tissue, respectively, were not associated with survival.
  
  
  CONCLUSIONS
  This U.S. based study found that telomeres may be longer in more aggressive HCCs. There was no evidence, however, that telomere length was associated with survival of patients with HCC. Future investigations are warranted to clarify the role of telomere length in HCC prognosis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: Baiyu
authors.initials: B
authors.lastname: Yang
authors.affiliation: Yale University School of Public Health, New Haven, CT, 06520, United States of America.
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Shebl
authors.affiliation: Pathology-Histotechnology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, United States of America.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Sternberg
authors.affiliation: Pathology-Histotechnology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, United States of America.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Warner
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Edelman
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: Allison
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892, United States of America.|Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD, 20892, United States of America.
authors.forename: Casey L
authors.initials: CL
authors.lastname: Dagnall
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892, United States of America.|Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research, Frederick, MD, 20892, United States of America.
authors.forename: Belynda D
authors.initials: BD
authors.lastname: Hicks
authors.affiliation: Division of Cancer Control & Population Sciences, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Altekruse
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI, 96813, United States of America.
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Hernandez
authors.affiliation: University of Iowa College of Public Health, Iowa City, IA, 52242, United States of America.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, 20892, United States of America.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McGlynn
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D003710:Demography; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D016615:Telomere / Q000378:metabolism*; D059506:Telomere Shortening