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Hepatitis B virus pre-S deletion mutations are a risk factor for hepatocellular carcinoma: a matched nested case–control study

¹ Department of Medicine, UCL Medical School, London W1T 4JF, UK
² Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Jin Zhou Road, Nanning, Guangxi 530028, PR China
³ Research Department of Infection and Population Health, Division of Population Health, UCL Medical School, University College London, London NW3 2PF, UK
⁴ Sanitary and Antiepidemic Station of Long An, ChengXi Road, Cheng Xiang Town, Long An, Guangxi 532700, PR China

Correspondence
Tim J. Harrison
t.harrison{at}ucl.ac.uk

A matched nested case–control study of 33 paired cases and controls was conducted, based on a study cohort in Long An county, Guangxi, China, to determine whether infection with hepatitis B virus (HBV) with pre-S deletions is independently associated with the development of hepatocellular carcinoma (HCC), without the confounding effects of basal core promoter (BCP) double mutations. The prevalence of pre-S deletions was significantly higher in HCC (45.5 %, 15 of 33) than the controls (18.2 %, 6 of 33) (P<0.01), under the control of the influence of BCP double mutations. Most of the pre-S deletions occurred in, or involved, the 5' half of the pre-S2 region and the difference between HCC (93.3 %, 14 of 15) and controls (66.7 %, four of six) was significant for this region (P=0.015). There was no significant difference in pre-S deletions between the BCP mutant group and BCP wild-type group (P>0.05), nor was the prevalence of pre-S deletions significantly different between genotypes B and C (P>0.1). These results suggest that pre-S deletions constitute an independent risk factor for HCC and their emergence and effect are independent of BCP mutations. The 5' terminus of pre-S2 is the favoured site for the deletion mutations, especially in HCC cases. Further prospective studies are required to confirm the role of these mutations in the development of HCC.

The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this study are FM211353–FM211418.

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