Skip to main content

Advertisement

SpringerLink
Log in

Association of glutathione S-transferase M1, T1, and P1 polymorphisms with renal cell carcinoma: evidence from 11 studies

  • Research Article
  • Published:
Tumor Biology

Abstract

The glutathione S-transferases (GSTs) are a gene superfamily of phase II metabolic enzymes that has attracted a considerable attention as a candidate gene for renal cell carcinoma (RCC) based on its enzyme function as a key factor in biotransformation pathways. In the past decade, a number of case–control studies were conducted to investigate the association of GST genetic polymorphisms and RCC risk. However, studies on the association between GST (GSTM1, GSTT1, and GSTP1) polymorphisms and RCC remain to be conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 2,189 cases and 3,817 controls from 11 case–control studies was performed. Overall, the summarized odds ratio for RCC of the GSTM1 null and GSTT1 null polymorphisms was 1.02 (95 % confidence interval (CI) 0.91–1.15, P = 0.70) and 1.28 (95 % CI 0.96–1.72, P = 0.09), respectively. No significant results were observed in heterozygous and homozygous genotypes when compared with wild-type genotype for GSTP1 I105V polymorphism. However, the GSTM1–GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with an increased RCC risk (odds ratio (OR) = 1.42, 95 % CI 1.14–1.76, P = 0.001). In the stratified analyses by ethnicity, significant gene–disease association was obtained among Asians for GSTT1 and GSTP1 polymorphisms. In our meta-analysis, the associations between variations of GSTs and RCC may vary in different ethnic populations, and the interaction between unfavorable GST genotypes may exist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Thrash-Bingham CA, Salazar H, Freed JJ, Greenberg RE, Tartof KD. Genomic alterations and instabilities in renal cell carcinomas and their relationship to tumor pathology. Cancer Res. 1995;55:6189–95.

    CAS  PubMed  Google Scholar 

  2. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med. 1996;335:865–75.

    Article  CAS  PubMed  Google Scholar 

  3. Lipworth L, Tarone RE, McLaughlin JK. The epidemiology of renal cell carcinoma. J Urol. 2006;176:2353–8.

    Article  PubMed  Google Scholar 

  4. McLaughlin JK, Chow WH, Mandel JS, Mellemgaard A, McCredie M, Lindblad P, et al. International renal-cell cancer study. VIII. Role of diuretics, other anti-hypertensive medications and hypertension. Int J Cancer. 1995;63:216–21.

    Article  CAS  PubMed  Google Scholar 

  5. Chow WH, Gridley G, Fraumeni Jr JF, Järvholm B. Obesity, hypertension and the risk of kidney cancer in men. N Engl J Med. 2000;343:1305–11.

    Article  CAS  PubMed  Google Scholar 

  6. Pesch B, Haerting J, Ranft U, Klimpel A, Oelschlägel B, Schill W. Occupational risk factors for renal cell carcinoma: agent-specific results from a case–control study in Germany. Int J Epidemiol. 2000;29:1014–24.

    Article  CAS  PubMed  Google Scholar 

  7. Benichou J, Chow WH, McLaughlin JK, Mandel JS, Fraumeni Jr JF. Population attributable risk of renal cell cancer in Minnesota. Am J Epidemiol. 1998;148:424–30.

    Article  CAS  PubMed  Google Scholar 

  8. McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene. 2006;25:1639–48.

    Article  CAS  PubMed  Google Scholar 

  9. Karami S, Boffetta P, Rothman N, Hung RJ, Stewart T, Zaridze D, et al. Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms. Carcinogenesis. 2008;29:1567–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Rebbeck TR. Molecular epidemiology of the human glutathione S-transferase genotypes and GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomark Prev. 1997;6:733–43.

    CAS  Google Scholar 

  11. Taningher M, Malacarne D, Izzotti A, Ugolini D, Parodi S. Drug metabolism polymorphisms as modulators of cancer susceptibility. Mutat Res. 1999;436:227–61.

    Article  CAS  PubMed  Google Scholar 

  12. Zimniak P, Nanduri B, Pikuła S, Bandorowicz-Pikuła J, Singhal SS, Srivastava SK, et al. Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties. Eur J Biochem. 1994;15:893–9.

    Article  Google Scholar 

  13. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  14. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Brüning T, Lammert M, Kempkes M, Thier R, Golka K, Bolt HM. Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with long-term high occupational exposure to trichloroethene. Arch Toxicol. 1997;71:596–9.

    Article  PubMed  Google Scholar 

  17. Longuemaux S, Deloménie C, Gallou C, Méjean A, Vincent-Viry M, Bouvier R, et al. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. Cancer Res. 1999;59:2903–8.

    CAS  PubMed  Google Scholar 

  18. Sweeney C, Farrow DC, Schwartz SM, Eaton DL, Checkoway H, Vaughan TL. Glutathione S-transferase M1, T1, and P1 polymorphisms as risk factors for renal cell carcinoma: a case–control study. Cancer Epidemiol Biomarkers Prev. 2000;9:449–54.

    CAS  PubMed  Google Scholar 

  19. Buzio L, De Palma G, Mozzoni P, Tondel M, Buzio C, Franchini I, et al. Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals. Occup Environ Med. 2003;60:789–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Moore LE, Brennan P, Karami S, Hung RJ, Hsu C, Boffetta P, et al. Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study. Carcinogenesis. 2007;28:1960–4.

    Article  CAS  PubMed  Google Scholar 

  21. Wiesenhütter B, Selinski S, Golka K, Brüning T, Bolt HM. Re-assessment of the influence of polymorphisms of phase-II metabolic enzymes on renal cell cancer risk of trichloroethylene-exposed workers. Arch Occup Environ Health. 2007;81:247–51.

    Article  Google Scholar 

  22. De Martino M, Klatte T, Schatzl G. Renal cell carcinoma Fuhrman grade and histological subtype correlate with complete polymorphic deletion of glutathione S-transferase M1 gene. J Urol. 2010;183:878–83.

    Article  PubMed  Google Scholar 

  23. Ahmad ST, Arjumand W, Seth A, Kumar Saini A, Sultana S. Impact of glutathione transferase M1, T1, and P1 gene polymorphisms in the genetic susceptibility of North Indian population to renal cell carcinoma. DNA Cell Biol. 2012;31:636–43.

    Article  CAS  PubMed  Google Scholar 

  24. Wang G, Hou J, Ma L. Risk factor for clear cell renal cell carcinoma in Chinese population: a case–control study. Cancer Epidemiol. 2012;36:177–82.

    Article  PubMed  Google Scholar 

  25. Salinas-Sánchez AS, Sánchez-Sánchez F, Donate-Moreno MJ. GSTT1, GSTM1, and CYP1B1 gene polymorphisms and susceptibility to sporadic renal cell cancer. Urol Oncol. 2012;30:864–70.

    Article  PubMed  Google Scholar 

  26. Hunt JD, van der Hel OL, McMillan GP, Boffetta P, Brennan P. Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer. 2005;114:101–8.

    Article  CAS  PubMed  Google Scholar 

  27. García-Closas M, Malats N, Silverman D, Dosemeci M, Kogevinas M, Hein DW, et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet. 2005;366:649–59.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Spurdle AB, Fahey P, Chen X, McGuffog L, kConFab, Easton D, et al. Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2010;122:281–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Ye Z, Song H, Higgins JP, Pharoah P, Danesh J. Five glutathione S-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies. PLoS Med. 2006;3:e91.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Saadat M. Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis. Cancer Sci. 2006;97:505–9.

    Article  CAS  PubMed  Google Scholar 

  31. 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. J Hepatol. 2010;53:508–18.

    Article  PubMed  Google Scholar 

  32. Mo Z, Gao Y, Cao Y, Gao F, Jian L. An updating meta-analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: a HuGE review. Prostate. 2009;69:662–88.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China

    Cheng-You Jia, Yu-Shui Ma, Da Fu & Zhong-Wei Lv

  2. Yueyang Hospital of Integrated Traditional Chinese & Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China

    Yu-Jin Liu

  3. Tissue Bank of China-Japan Union Hospital, Ji Lin University, Changchun, 130033, People’s Republic of China

    Xian-Ling Cong & Ran Sun

Authors
  1. Cheng-You Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu-Jin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xian-Ling Cong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-Shui Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ran Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Da Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhong-Wei Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Da Fu or Zhong-Wei Lv.

Additional information

Cheng-You Jia and Yu-Jin Liu contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary figure 1

(DOC 185 kb)

Supplementary figure 2

(DOC 515 kb)

Supplementary figure 3

(DOC 527 kb)

Supplementary figure 4

(DOC 412 kb)

Supplementary figure 5

(DOC 401 kb)

Supplementary figure 6

(DOC 67 kb)

Supplementary figure 7

(DOC 67.5 kb)

Supplementary figure 8

(DOC 67 kb)

Supplementary figure 9

(DOC 67 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jia, CY., Liu, YJ., Cong, XL. et al. Association of glutathione S-transferase M1, T1, and P1 polymorphisms with renal cell carcinoma: evidence from 11 studies. Tumor Biol. 35, 3867–3873 (2014). https://doi.org/10.1007/s13277-013-1513-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1513-5

Keywords

Search

Navigation