Abstract 4462: Relative telomere length in circulating serum DNA as a novel non-invasive biomarker in hepatocarcinogenesis
Authors: Wan Shaogui , Hann Hie-Won , Fu Xiaoying , Myers Ronald E. , Hann Richard S. , Au Jenifer , Chen Bicui , Tang Heng , Xing Jinliang , Yang Hushan 
Published: August 2012

Abstract
Background: Abnormal telomere maintenance has been significantly implicated in tumor development and progression. Telomere length has recently emerged as a promising predictor for the risk of various cancers including hepatocellular carcinoma (HCC). Nonetheless, no studies have been reported on measuring telomere length in circulating cell-free DNA samples as a non-invasive biomarker of cancer risk. Method: In this nested case-control study, we used real-time quantitative PCR to determine the relative telomere length (RTL) in serum DNA samples from 140 hepatitis B virus (HBV)-related HCC (HBV-HCC) cases and 280 frequency-matched cancer-free HBV controls, and evaluated the associations between RTL and HBV-HCC risk, as well as RTL and HBV-cirrhosis risk in a sub-population of 100 HBV-cirrhosis cases and 100 matched HBV controls. Results: We found that HBV-HCC cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) versus HBV controls (median, 0.20; range, 0.01-1.60) (P=0.003). Using the median RTL value in controls as the cutoff point, individuals with longer RTLs exhibited a significantly increased risk of HCC compared to those with short RTLs in an univariate logistic regression analysis (odds ratio [OR]=1.55, 95% confidence interval [CI] 1.02-2.33, P=0.038). However, the strength of 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 the univariate analysis (P trend=0.017) which was attenuated in the multivariate analysis (P trend=0.079). Further analyses revealed that the significant association between serum RTL and HCC risk was only evident in non-cirrhotic (OR=3.54, 95% CI 1.58-7.93 P=0.002), but not in cirrhotic (OR=0.95, 95% CI 0.55-1.64, P=0.860) HBV patients. Additionally, a significant difference (P=0.004) of RTL distribution was observed between cirrhotic and non-cirrhotic HBV controls. We further analyzed the association of RTL with liver cirrhosis risk. Using patients with short RTL as reference, we found long RTL conferred a significantly increased risk of HBV-related cirrhosis in univariate and multivariate analyses with unadjusted OR of 2.70 (95% CI 1.50-4.88, P=0.001) and 2.73 (95% CI 1.51-4.93, P=0.001), respectively. Further tertile and quartile analysis showed a significant dose-response relationship (P trend &lt;0.001 for both) in both univariate and multivariate analysis. Conclusions: Collectively, our data suggested that RTL in circulating cell-free serum DNA could potentially be used as a novel non-invasive biomarker for non-cirrhotic HBV-HCC and HBV-related cirrhosis. Prospective cohort studies are warranted to further validate this finding and assess its clinical significance in HCC prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4462. doi:1538-7445.AM2012-4462