Longer Leukocyte Telomere Length Predicts Increased Risk of Hepatitis B Virus-Related Hepatocellular Carcinoma A Case-Control Analysis

BACKGROUND: Convincing evidence has indicated that an alteration in telomere length is involved in tumorigenesis. In epidemiologic studies, a strong correlation also has been observed consistently between relative telomere length (RTL) in peripheral blood leukocytes (PBLs) and susceptibility of many cancers. However, whether leukocyte RTL can be used as a predictor of risk for hepatocellular carcinoma (HCC) remains to be determined. METHODS: The RTL in PBLs was determined by measuring the telomere repeat copy number to single-copy gene number ratio in each sample compared with a reference DNA sample using a polymerase chain reaction-based method in this case-control study. The study participants included 240 patients with HCC (cases), a group of 240 healthy individuals (controls), and 120 noncancer controls with chronic liver disease (CLD). RESULTS: HCC cases exhibited a significantly longer RTL (median, 0.57; range, 0.21-3.3) than CLD controls (median, 0.46; range, 0.15-1.99; P < .001) and healthy controls (median, 0.39; range, 0.13-2.69; P < .001). Compared with individuals who had short RTL, individuals who had long RTL had a significantly increased risk of HCC when either healthy controls (adjusted odds ratio [OR], 7.28; 95% confidence interval, 4.46-11.88) or CLD controls (adjusted OR, 2.86; 95% confidence interval, 1.74-4.70) were used as the reference group. A significant dose-response relation was observed between HCC risk and long RTL (P-trend < .001 for both control groups). In addition, there was a significantly positive RTL correlation between PBLs and normal liver tissues (r = 0.78; P < .001) or cirrhotic liver tissues (r = 0.67; P = .001). Furthermore, a significant joint effect on the risk of HCC was noted between RTL and smoking status or alcohol use. CONCLUSIONS: The current study produced the first epidemiologic evidence linking long RTL in PBLs to an increased risk of HCC. The authors concluded that these findings warrant further investigation in other populations. Cancer 2011;117:4247-56. (C) 2011 American Cancer Society.