Tumor Biology

, Volume 35, Issue 1, pp 501–505 | Cite as

RETRACTED ARTICLE: Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis

  • Hong-Li Sun
  • Bing Han
  • Hong-Peng Zhai
  • Xin-Hua Cheng
  • Kai Ma
Research Article


Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95 % confidence interval (95 % CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR = 1.13, 95 % CI 0.88–1.46, P = 0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR = 1.46, 95 % CI 1.02–2.09, P = 0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.


Gallbladder cancer GSTM1 Meta-analysis 


Conflicts of interest



  1. 1.
    Eslick GD. Epidemiology of gallbladder cancer. Gastroenterol Clin North Am. 2010;39(2):307–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Zhu AX, Hong TS, Hezel AF, Kooby DA. Current management of gallbladder carcinoma. The Oncologist. 2010;15:168–81.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Jayaraman S, Jarnagin WR. Management of gallbladder cancer. Gastroenterol Clin North Am. 2010;39(2):331–42.CrossRefPubMedGoogle Scholar
  4. 4.
    Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. Journal of Clinical Oncology. 2012;30:1934–40.CrossRefPubMedGoogle Scholar
  5. 5.
    Mishra RR, Tewari M, Shukla HS. Helicobacter species and pathogenesis of gallbladder cancer. Hepatobiliary & Pancreatic Diseases International. 2010;9:129–34.Google Scholar
  6. 6.
    Marsh Rde W, Alonzo M, Bajaj S, Baker M, Elton E, Farrell TA. Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part I: diagnosis-clinical staging and pathology. Journal of Surgical Oncology. 2012;106:332–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Rai R, Tewari M, Kumar M, Singh AK, Shukla HS. P53: its alteration and gallbladder cancer. European Journal of Cancer Prevention. 2011;20:77–85.CrossRefPubMedGoogle Scholar
  8. 8.
    Srivastava K, Srivastava A, Sharma KL, Mittal B. Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis. Mutation Research. 2011;728:67–79.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Dong LM, Potter JD, White E, Ulrich CM, Cardon LR, Peters U. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. Journal of the American Medical Association. 2008;299:2423–36.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annual Review of Pharmacology and Toxicology. 2005;45:51–88.CrossRefPubMedGoogle Scholar
  11. 11.
    Oakley A. Glutathione transferases: a structural perspective. Drug Metabolism Reviews. 2011;43:138–51.CrossRefPubMedGoogle Scholar
  12. 12.
    Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology. 2000;61:154–66.CrossRefPubMedGoogle Scholar
  13. 13.
    Strange RC, Spiteri MA, Ramachandran S, Fryer AA. Glutathione-S-transferase family of enzymes. Mutation Research. 2001;482:21–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Pandey SN, Jain M, Nigam P, Choudhuri G, Mittal B. Genetic polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3 and the susceptibility to gallbladder cancer in north India. Biomarkers. 2006;11:250–61.CrossRefPubMedGoogle Scholar
  15. 15.
    Kimura A, Tsuchiya Y, Lang I, Zoltan S, Nakadaira H, Ajioka Y, et al. Effect of genetic predisposition on the risk of gallbladder cancer in Hungary. Asian Pacific Journal of Cancer Prevention. 2008;9:391–6.PubMedGoogle Scholar
  16. 16.
    Gao J, Liang G, Cheng J, Deng J, Wang BS. Relationship between polymorphisms of DNA repair genes and glutathione-s-transferase genes and risk of biliary tract cancer. TUMOR. 2009;29:145–51.Google Scholar
  17. 17.
    Tsuchiya Y, Baez S, Calvo A, Pruyas M, Nakamura K, Kiyohara C, et al. Evidence that genetic variants of metabolic detoxication and cell cycle control are not related to gallbladder cancer risk in Chilean women. The International Journal of Biological Markers. 2010;25:75–8.PubMedGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  20. 20.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. Journal of the National Cancer Institute. 1959;22:719–48.PubMedGoogle Scholar
  21. 21.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Marahatta SB, Punyarit P, Bhudisawasdi V, Paupairoj A, Wongkham S, Petmitr S. Polymorphism of glutathione S-transferase omega gene and risk of cancer. Cancer Letters. 2006;236:276–81.CrossRefPubMedGoogle Scholar
  23. 23.
    Tsuchiya Y, Kiyohara C, Sato T, Nakamura K, Kimura A, Yamamoto M. Polymorphisms of cytochrome p450 1a1, glutathione S-transferase class mu, and tumour protein p53 genes and the risk of developing gallbladder cancer in Japanese. Clinical Biochemistry. 2007;40:881–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Liu Y, Xu LZ. Meta-analysis of association between GSTM1 gene polymorphism and cervical cancer. Asian Pacific Journal of Tropical Medicine. 2012;5:480–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Wang B, Huang G, Wang D, Li A, Xu Z, Dong R, et al. Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis. Journal of Hepatology. 2010;53:508–18.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhang R, Xu G, Chen W, Zhang W. Genetic polymorphisms of glutathione S-transferase M1 and bladder cancer risk: a meta-analysis of 26 studies. Molecular Biology Reports. 2011;38:2491–7.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Hong-Li Sun
    • 1
  • Bing Han
    • 1
  • Hong-Peng Zhai
    • 2
  • Xin-Hua Cheng
    • 1
  • Kai Ma
    • 1
  1. 1.Department of Biliary and Vascular SurgeryChina Medical University Affiliated Shengjing HospitalShenyangChina
  2. 2.Department of General SurgeryFengtian Hospital of Shenyang Medical CollegeShenyangChina

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