1. ¹Cell Injury and Apoptosis Group, Edinburgh MRC Centre for Inflammation Research, College of Medicine and Veterinary Medicine, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK
2. ²Department of Surgery, Division of Hepato-biliary and Pancreatic Surgery, Chinese University of Hong Kong, Hong Kong SAR, China

Correspondence: Dr JA Ross, E-mail: J.A.Ross@ed.ac.uk

³Wheelhouse's current address: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, Scotland

Received 4 November 2004; Revised 7 February 2005; Accepted 8 February 2005; Published online 22 March 2005.

Abstract

The largest single underlying cause of hepatocellular carcinoma (HCC) worldwide is hepatitis B virus (HBV) infection. Hepatitis B virus increases cellular oxidative stress and the development of HCC occurs after a long latency period. The study was carried out to determine whether mitochondrial DNA abnormalities were associated with HCC in individuals with HBV. The frequency of mutation and deletion of specific areas of the mitochondrial genome in tumour and matched normal tissue of patients with HBV infection was investigated in the current study. The percentage of control subjects harbouring D-loop mutations was 11%, which was significantly lower than that observed in both the noncancerous (49%, P=0.033) and tumour tissue (59%, P=0.014) of patients with HCC. In contrast, the number of cases in which the common 4977 bp deletion of the mitochondrial genome was detected was significantly greater in control liver and noncancerous liver tissue of subjects with HCC (100 and 95%, respectively) than in cancerous liver tissue (28%, P<0.001). These observations suggest that the inflammatory process contributes to the rate of mitochondrial mutations. However, the lower frequency of the large deletion in cancerous tissue suggests that there is selection against either mitochondria, which harbour large deletions, or against cells that contain these mitochondria during hepatocarcinogenesis.