title: Relative telomere length: a novel non-invasive biomarker for the risk of non-cirrhotic hepatocellular carcinoma in patients with chronic hepatitis B infection.
abstract: OBJECTIVE
  Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.
  
  
  METHODS
  We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.
  
  
  RESULTS
  Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls (median, 0.20; range, 0.01-1.60) (P = 0.003). Consistently, longer RTLs conferred a significantly increased HCC risk compared to short RTLs in a univariate logistic regression analysis (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.02-2.33, P = 0.038). This association attenuated after multivariate adjustment (OR = 1.40, 95% CI = 0.90-2.19, P = 0.132). In a quartile analysis, a significant dose-response relationship was noted in univariate analysis (P(trend) = 0.017) which was again attenuated in multivariate analysis (P(trend) = 0.079). Further analyses revealed that the significant association between serum RTL and HCC risk was evident in non-cirrhotic (OR = 3.54, 95% CI 1.58-7.93 P = 0.002), but not cirrhotic (OR = 0.95, 95% CI 0.55-1.64, P = 0.860) HBV patients. Moreover, the significantly increased HCC risk conferred by cirrhosis was modulated by RTL with a significant interaction effect (P(interaction) = 0.013).
  
  
  CONCLUSIONS
  RTL in circulating cell-free serum DNA could potentially be used as a novel non-invasive biomarker for non-cirrhotic HCC. Prospective cohort studies are warranted to validate this finding and assess its clinical significance in HCC prevention.
authors.affiliation: Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
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: Richard S
authors.initials: RS
authors.lastname: Hann
authors.forename: Jennifer
authors.initials: J
authors.lastname: Au
authors.forename: Bicui
authors.initials: B
authors.lastname: Chen
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
mesh_terms: D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D044967:Serum / Q000737:chemistry*; D059505:Telomere Homeostasis
chemical_list: D015415:Biomarkers