Tumor Biology

, Volume 33, Issue 4, pp 1059–1063 | Cite as

RETRACTED ARTICLE: Joint effect of polymorphism in the N-acetyltransferase 2 gene and smoking on hepatocellular carcinoma

Research Article

Abstract

The N-acetyltransferase 2 gene (NAT2) has been implicated in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between NAT2 polymorphism and HCC risk. Published literatures from PubMed, EMBASE, CNKI, and Wan Fang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies including 1,084 HCC cases and 1,682 controls were identified for the data analysis. The overall result showed that there was no statistically significant association between NAT2 genotypes and HCC risk (slow acetylation vs. rapid/intermediate acetylation: OR = 1.03, 95% CI 0.86–1.24). In the stratified analyses, NAT2 genotypes were also not significantly associated with HCC risk among both Europeans (OR = 1.11, 95% CI 0.86–1.43) and East Asians (OR = 1.01, 95% CI 0.65–1.56). Further subgroup analyses based on the smoking status showed that the effect size was statistically significant among the smokers (OR = 2.09, 95% CI 1.07–4.09), but not among those who never smoked (OR = 1.26, 95% CI 0.88–1.82). The present meta-analysis indicated that NAT2 genotypes were not associated with increased risk of HCC among the overall population but increased the risk of HCC among the smokers.

Keywords

N-acetyltransferase 2 gene Polymorphism Hepatocellular carcinoma Meta-analysis 

Notes

Conflict of interest

None.

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Smith CA, Smith G, Wolf CR. Genetic polymorphisms in xenobiotic metabolism. Eur J Cancer. 1994;30A:1921–35.CrossRefPubMedGoogle Scholar
  3. 3.
    Agúndez JA, Olivera M, Ladero JM, Rodriguez-Lescure A, Ledesma MC, Diaz-Rubio M, et al. Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. Pharmacogenetics. 1996;6:501–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Yu MW, Pai CI, Yang SY, Hsiao TJ, Chang HC, Lin SM, et al. Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk. Gut. 2000;47:703–9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Agúndez JA, Ladero JM, Olivera M, Lozano L, Fernández-Arquero M, de laConcha EG, et al. N-acetyltransferase 2 polymorphism is not related to the risk of advanced alcoholic liver disease. Scand J Gastroenterol. 2002;37:99–103.CrossRefPubMedGoogle Scholar
  6. 6.
    Gao JP, Huang YD, Lin JA, Zhu QC, Liang JP. Relationship between genetic polymorphisms of N-acetyltransferase and susceptibility to hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 2003;11:20–2.PubMedGoogle Scholar
  7. 7.
    Huang YS, Chern HD, Wu JC, Chao Y, Huang YH, Chang FY, et al. Polymorphism of the N-acetyltransferase 2 gene, red meat intake, and the susceptibility of hepatocellular carcinoma. Am J Gastroenterol. 2003;98:1417–22.CrossRefPubMedGoogle Scholar
  8. 8.
    Farker K, Schotte U, Scheele J, Hoffmann A. Impact of N-acetyltransferase polymorphism (NAT2) in hepatocellular carcinoma (HCC)—an investigation in a department of surgical medicine. Exp Toxicol Pathol. 2003;54:387–91.CrossRefPubMedGoogle Scholar
  9. 9.
    Zhang XY. Study on environmental risk factors and genetic susceptibility of hepatocellular carcinoma in Luo Yang, China. Master's thesis of Fudan University. 2003, 1–73.Google Scholar
  10. 10.
    Gelatti U, Covolo L, Talamini R, Tagger A, Barbone F, Martelli C, et al. N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study. Int J Cancer. 2005;115:301–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Imaizumi T, Higaki Y, Hara M, Sakamoto T, Horita M, Mizuta T, et al. Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population. Carcinogenesis. 2009;30:1729–34.CrossRefPubMedGoogle Scholar
  12. 12.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  13. 13.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  14. 14.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.CrossRefPubMedGoogle Scholar
  15. 15.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hietanen E, Husgafvel-Pursiainen K, Vainio H. Interaction between dose and susceptibility to environmental cancer: a short review. Environ Health Perspect. 1997;105:749–54.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Chen CJ, Yu MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12:294–308.CrossRefGoogle Scholar
  18. 18.
    Blum HE. Hepatocellular carcinoma: susceptibility markers. IARC Sci Publ. 2001;154:241–4.PubMedGoogle Scholar
  19. 19.
    Farker K, Schotte U, Scheele J, Hoffmann A. Assessment of frequencies of lifestyle factors and polymorphisms of drug-metabolizing enzymes (NAT2, CYP2E1) in human hepatocellular carcinoma (HCC) patients in a department of surgical medicine–a pilot investigation. Int J Clin Pharmacol Ther. 2002;40:120–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Ying XJ, Dong P, Shen B, Wang J, Wang S, Wang G. Possible association of NAT2 polymorphism with laryngeal cancer risk: an evidence-based meta-analysis. J Cancer Res Clin Oncol. 2011;137:1661–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang J, Qiu LX, Wang ZH, Wang JL, He SS, Hu XC. NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat. 2010;123:877–83.CrossRefPubMedGoogle Scholar
  22. 22.
    Sanderson S, Salanti G, Higgins J. Joint effects of the N-acetyltransferase 1 and 2 (NAT1 and NAT2) genes and smoking on bladder carcinogenesis: a literature-based systematic HuGE review and evidence synthesis. Am J Epidemiol. 2007;166:741–51.CrossRefPubMedGoogle Scholar
  23. 23.
    Cui D, Wang Z, Zhao E, Ma J, Lu W. NAT2 polymorphism and lung cancer risk: a meta-analysis. Lung Cancer. 2011;73:153–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Zhong X, Hui C, Xiao-Ling W, Yan L, Na L. NAT2 polymorphism and gastric cancer susceptibility: a meta-analysis. Arch Med Res. 2010;41:275–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Gong C, Hu X, Gao Y, Cao Y, Gao F, Mo Z. A meta-analysis of the NAT1 and NAT2 polymorphisms and prostate cancer: a huge review. Med Oncol. 2011;28:365–76.CrossRefPubMedGoogle Scholar
  26. 26.
    Raimondi S, Botteri E, Iodice S, Lowenfels AB, Maisonneuve P. Gene–smoking interaction on colorectal adenoma and cancer risk: review and meta-analysis. Mutat Res. 2009;670:6–14.CrossRefPubMedGoogle Scholar
  27. 27.
    Pfau W, Stone EM, Brockstedt U, Carmichael PL, Marquardt H, Phillips DH. DNA adducts in human breast tissue: association with N-acetyltransferase-2 (NAT2) and NAT1 genotypes. Cancer Epidemiol Biomarkers Prev. 1998;7:1019–25.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  1. 1.Department of Gastroenterology, The Second Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of General Surgery, The Second Xiangya HospitalCentral South UniversityChangshaChina

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