Abstract
Background and aimsTelomere 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. MethodsWe 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. ResultsCases 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 (Ptrend=0.017) which was again attenuated in multivariate analysis (Ptrend=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 (Pinteraction=0.013). ConclusionsRTL 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.
Highlights
In the United States, the incidence of new acute HBV infection decreased over the past two decades, the number of patients living with chronic HBV infection has grown significantly
Longer relative telomere length (RTL) conferred a significantly increased hepatocellular carcinoma (HCC) risk compared to short RTLs in a univariate logistic regression analysis
Further analyses revealed that the significant association between serum RTL and HCC risk was evident in non-cirrhotic (OR=3.54, 95% confidence intervals (95% CIs) 1.58–7.93 P=0.002), but not cirrhotic (OR=0.95, 95% CI 0.55–1.64, P=0.860) HBV
Summary
In the United States, the incidence of new acute HBV infection decreased over the past two decades, the number of patients living with chronic HBV infection has grown significantly. This development is partly due to the trend of increasing immigration from areas with high HBV endemicity such as Asian and Sub-Arab countries [1]. In addition to the end replication issue, other factors such as oxidative stress, chronic inflammation, and loss of telomere binding proteins may contribute to telomere shortening and lead to the tumorigenesis of many solid cancers including HCC [8,9,10]. No studies have been reported on using circulating DNA telomere length as a noninvasive HCC biomarker
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