Background & Aims
Southern Guangxi area is one of the endemic areas for hepatocellular carcinoma (HCC)
in China. This study evaluates the roles of genetic variations of hepatitis B virus
(HBV) and aflatoxin B1 (AFB1) exposure in the formation of HCC in this high-risk area.
Methods
The study recruited 60 HCC patients and 120 age-, gender-, and residency-matched controls.
HBV genotype and basic core promoter (BCP) mutations were determined by nested-PCR/direct
sequencing. Serum AFB1-lysine adduct was measured by high performance liquid chromatography-fluorescence
detection.
Results
HBV genotype C was predominant in 75.0% of cases and 84.2% of controls. The 1762T/1764A double mutations, 1753V mutations, and 1752V mutations were associated with HCC risk evidenced by the adjusted odds ratio (OR)
[95% confidence interval (95% CI)] of 3.89 (1.40–10.77), 2.87 (1.49–5.49), and 5.96
(1.75–20.25), respectively. The adjusted OR (95% CI) was 6.94 (1.68–27.78) for subjects
with 1762T/1764A double mutations and high AFB1-lysine adduct level; 2.01 (0.24–14.29), for those with only 1762T/1764A double mutations; and 4.26 (1.16–15.38) for those with only high AFB1-lysine adduct level, respectively. The adjusted OR was 5.13 (1.79–14.71) for subjects
with 1753V mutations and high AFB1-lysine adduct level; 1.20 (0.47–3.08) for those with only 1753V mutations, and 2.28 (1.01–5.31) for those with high AFB1-lysine adduct level, respectively.
Conclusions
These data confirmed the association of BCP mutations with HCC risk and the additive
effects of 1762T/1764A double mutations and 1753V mutations with dietary AFB1 exposure in this high-risk area for HCC.
Abbreviations:
HBV (hepatitis B virus), AFB1 (aflatoxin B1), HCC (hepatocellular carcinoma), BCP (basic core promoter), OR (odds ratio), CI (confidence interval), AF (aflatoxin), HCV (hepatitis C virus), IARC (International Agency for Research on Cancer), HBsAg (HBV surface antigen), HPLC (high performance liquid chromatography), nPCR (nested polymerase chain reaction)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global cancer facts & figures 2007.American Cancer Society, Atlanta, GA2007
- Hepatitis B viral genotypes: clinical relevance and molecular characteristics.J Gastroenterol Hepatol. 2002; 17: 643-650
- Specific mutations of hepatitis B virus in plasma predict liver cancer development.Proc Natl Acad Sci USA. 2004; 101: 3575-3580
- Classifying hepatitis B virus genotypes.Intervirology. 2003; 46: 329-338
- Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma.Gut. 2004; 53: 1494-1498
- The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis (Review).Int J Oncol. 1999; 15: 373-379
- Wild-type levels of pregenomic RNA and replication but reduced pre-C RNA and e-antigen synthesis of hepatitis B virus with C(1653) → T, A(1762) → T and G(1764) → A mutations in the core promoter.J Gen Virol. 1998; 79: 375-380
- Effect of basal core promoter and pre-core mutations on hepatitis B virus replication.J Gen Virol. 2008; 89: 901-909
- HBV A1762T, G1764A mutations are a valuable biomarker for identifying a subset of male HBsAg carriers at extremely high risk of hepatocellular carcinoma: a prospective study.Am J Gastroenterol. 2008; 103: 2254-2262
- Prospective evaluation of hepatitis B 1762(T)/1764(A) mutations on hepatocellular carcinoma development in Shanghai, China.Cancer Epidemiol Biomarkers Prev. 2009; 18: 590-594
- Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometry.Cancer Epidemiol Biomarkers Prev. 2007; 16: 1213-1218
- Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas from Thailand.Cancer Epidemiol Biomarkers Prev. 2005; 14: 380-384
- T1762/A1764 variants of the basal core promoter of hepatitis B virus; serological and clinical correlations in Chinese patients.Liver. 1999; 19: 411-417
- Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma.J Hepatol. 2006; 45: 646-653
- Clinical implications of mutations C-to-T1653 and T-to-C/A/G1753 of hepatitis B virus genotype C genome in chronic liver disease.Arch Virol. 1999; 144: 1299-1308
- Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels.Gut. 2008; 57: 98-102
- Risk factors for hepatocellular carcinoma in Guangxi, People’s Republic of China.Natl Cancer Inst Monogr. 1985; 69: 47-48
- Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China.Cancer Res. 1989; 49: 2506-2509
- Low prevalence of hepatitis C infection in hepatocellular carcinoma (HCC) cases and population controls in Guangxi, a hyperendemic region for HCC in the People’s Republic of China.Br J cancer. 1996; 74: 491-493
- Monitoring of aflatoxin exposure by biomarkers.J Toxicol Sci. 1998; 23: 155-159
- Aflatoxin and hepatitis B virus biomarkers: a paradigm for complex environmental exposures and cancer risk.Cancer Biomark. 2005; 1: 5-14
- A web-based genotyping resource for viral sequences.Nucleic Acids Res. 2004; 32: W654-W659
- Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People’s Republic of China.Cancer Epidemiol Biomarkers Prev. 1996; 5: 253-261
- The impact of confounder selection criteria on effect estimation.Am J Epidemiol. 1989; 129: 125-137
- Role of hepatitis B virus genotype mixture, subgenotypes C2 and B2 on hepatocellular carcinoma: compared with chronic hepatitis B and asymptomatic carrier state in the same area.Carcinogenesis. 2008; 29: 1685-1691
- Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China.J Viral Hepat. 2005; 12: 609-617
- A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China.J Med Virol. 2009; 81: 1517-1524
- Prevalence of hepatitis B virus subgenotypes and basal core promoter, precore variants in patients with acute hepatitis B in central Vietnam.Intervirology. 2009; 52: 22-28
- Genotype and variations in core promoter and pre-core regions are related to progression of disease in HBV-infected patients from Northern Vietnam.Int J Mol Med. 2007; 19: 293-299
- Hepatitis B virus genotypes, phylogeny and occult infection in a region with a high incidence of hepatocellular carcinoma in China.World J Gastroenterol. 2004; 10: 3264-3268
- Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma.Gastroenterology. 2004; 127: 1733-1738
- Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China.J Hepatol. 2008; 49: 718-725
- A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV Genotype Research Group.Hepatology. 2001; 33: 218-223
- Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma.J Natl Cancer Inst. 2008; 100: 1134-1143
- High prevalence of 1762(T) 1764(A) mutations in the basic core promoter of hepatitis B virus isolated from black Africans with hepatocellular carcinoma compared with asymptomatic carriers.Hepatology. 1999; 29: 946-953
IARC. Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. 1993;245–395.
- Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma.Lancet. 1992; 339: 943-946
- Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan.Int J Cancer. 1996; 67: 620-625
- Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma.Hepatology. 1996; 24: 38-42
- A model of interaction: aflatoxins and hepatitis viruses in liver cancer aetiology and prevention.Cancer Lett. 2009; 286: 22-28
- Molecular dosimetry of urinary aflatoxin-DNA adducts in people living in Guangxi Autonomous Region, People’s Republic of China.Cancer Res. 1992; 52: 45-52
- Hepatocellular carcinoma and aflatoxin exposure in Zhuqing Village, Fusui County, People’s Republic of China.Cancer Epidemiol Biomarkers Prev. 2001; 10: 143-146
Article info
Publication history
Published online: June 29, 2010
Accepted:
April 8,
2010
Received in revised form:
March 18,
2010
Received:
January 20,
2010
Identification
Copyright
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.