Longer leukocyte telomere length predicts increased risk of hepatitis b virus-related hepatocellular carcinoma

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Original Article

Longer leukocyte telomere length predicts increased risk of hepatitis b

virus-related hepatocellular carcinoma

A case-control analysis

Liu MD1,†, Yefa Yang MD2,†, Hongxin Zhang MD3, Siyuan Zhao MD3, Hanqiang

Liu MD1, Naijian Ge MD2, Hushan Yang PhD4, Jin-Liang Xing MD, PhD1,*,‡, Zhinan

Chen MD, PhD1Article first published online: 8 MAR 2011

DOI: 10.1002/cncr.26015

Copyright © 2011 American Cancer Society

Issue

Cancer

Early View (Articles online in advance of print)

Abstract

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 (Ptrend < .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;. © 2011

American Cancer Society.