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Liver disease
Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk
  1. M-W Yua,
  2. C-I Paia,
  3. S-Y Yanga,
  4. T-J Hsiaob,
  5. H-C Changa,
  6. S-M Linc,
  7. Y-F Liawc,
  8. P-J Chend,
  9. C-J Chena
  1. aGraduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan, bDepartment of Internal Medicine, Provincial Taoyuan General Hospital, Taoyuan, Taiwan, cLiver Research Unit, Chang-Gung Memorial Hospital, Chang-Gung University, Taipei, Taiwan, dDepartment of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  1. Dr M-W Yu, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, No 1 Jen-Ai Road Section 1, Room 1550, Taipei 100, Taiwan.mingwhei{at}ha.mc.ntu.edu.tw

Abstract

BACKGROUND Persistent infection with hepatitis B virus (HBV) causes chronic phasic necroinflammation and regenerative proliferation in the liver. The sustained hepatocellular proliferation may render chronic HBV carriers more susceptible to the effects of environmental carcinogens. Aromatic amines are potential hepatocarcinogens in humans.N-acetyltransferase (NAT) is involved in the metabolic activation and detoxification of these compounds.

AIMS To investigate if genetic polymorphisms in N-acetylation are related to hepatocellular carcinoma (HCC) among chronic HBV carriers.

METHODS Genotyping ofNAT1 and NAT2 was performed using polymerase chain reaction-restriction fragment length polymorphism on peripheral leucocyte DNA from 151 incident cases of HCC and 211 controls. All subjects were male, and were chronic HBV surface antigen carriers.

RESULTS A significant association between NAT2 genetic polymorphism and HCC was observed among chronic HBV carriers who were smokers but not among those who were non-smokers. For smoking HBV carriers, the odds ratios of developing HCC for those heterozygous and homozygous for the NAT2*4 functional allele compared with those without any copies of the functional allele (reference group) were 2.67 (95% confidence interval 1.15–6.22) and 2.58 (95% confidence interval 1.04–6.43), respectively. The interaction between cigarette smoking and the presence of theNAT2*4 allele just failed to reach statistical significance (p=0.06). No association betweenNAT1 genotype and HCC was evident overall or within the smoking stratified subgroups.

CONCLUSIONS Our results suggest that NAT2 activity may be particularly critical in smoking related hepatocarcinogenesis among chronic HBV carriers. Our data also indirectly support a role for tobacco smoke derived aromatic amines in the aetiology of HCC.

  • genetic polymorphism
  • hepatocellular carcinoma
  • N-acetyltransferase
  • smoking

  • Abbreviations used in this paper

    HBV
    hepatitis B virus
    HBsAg
    hepatitis B surface antigen
    HCC
    hepatocellular carcinoma
    NAT
    N-acetyltransferase
    OR
    odds ratio
    PCR-RFLP
    polymerase chain reaction-restriction fragment length polymorphism

    • https://doi.org/10.1136/gut.47.5.703

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    • Abbreviations used in this paper

      HBV
      hepatitis B virus
      HBsAg
      hepatitis B surface antigen
      HCC
      hepatocellular carcinoma
      NAT
      N-acetyltransferase
      OR
      odds ratio
      PCR-RFLP
      polymerase chain reaction-restriction fragment length polymorphism
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