title: Telomere length in circulating serum DNA as a novel non-invasive biomarker for cirrhosis: a nested case-control analysis.
abstract: OBJECTIVE
  Previous studies have indicated that telomere length is associated with altered risk of various tumours including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the association between telomere length and the risk of cirrhosis has not been reported.
  
  
  METHODS
  In this nested case-control study, we used real-time quantitative PCR to determine the relative telomere length (RTL) in serum DNA samples from 100 HBV-related cirrhosis cases and 100 frequency-matched HBV controls, and evaluated the associations between RTL and cirrhosis risk by logistic regression analyses.
  
  
  RESULTS
  We found that cirrhotic cases had a significantly longer RTL (median, 0.36; range, 0.08-1.87) than non-cirrhotic controls (median, 0.20; range, 0.05-1.11) (P < 0.0001). Compared with subjects with short RTL, those with long RTL had a significantly increased cirrhosis risk [odds ratio, 2.76, 95% confidence interval, 1.50-5.10; P = 0.001]. Quartile analysis further indicated a dose-response effect for this association. Compared with patients with the lowest quartile of RTL, the cirrhosis risk for those with the second, third and highest quartile of RTL was 2.68 (0.91-7.87, P = 0.073), 3.37 (1.32-10.54, P = 0.013) and 6.64 (2.41-18.32, P < 0.0001) respectively (P(trend) <0.0001). Moreover, the area under the receiver operating characteristic curve increased from 0.60 (epidemiological variables) to 0.72 (epidemiological variables plus RTL), with statistically significant difference assessed by bootstrap analysis.
  
  
  CONCLUSIONS
  Our study presents the first epidemiological evidence that RTL in serum DNA could potentially be used as a simple, inexpensive and non-invasive marker of cirrhosis risk, a finding that warrants further investigations in independent retrospective and prospective populations.
authors.affiliation: Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, PA 19107, USA.
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hann
authors.forename: Su H
authors.initials: SH
authors.lastname: Kim
authors.forename: Heng
authors.initials: H
authors.lastname: Tang
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000097:blood; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D016615:Telomere / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D004247:DNA