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Re-assessment of the influence of polymorphisms of phase-II metabolic enzymes on renal cell cancer risk of trichloroethylene-exposed workers

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Abstract

Problem

Individual differences in susceptibility to trichloroethylene-induced nephrocarcinogenicity may be conferred by genetic polymorphisms of glutathione S-transferases (GST), because enzymes of this group are pivotal for the metabolic activation of trichloroethylene. Because of a potential involvement of N-acetylation in the detoxication of reactive trichloroethylene metabolite(s) to N-acetyl-cysteine derivatives, polymorphisms of the NAT2 gene may also be relevant.

Methods

The primary collective used for a re-investigation of these questions was that of a hospital-based case-control study by Brüning et al. (Am J Ind Med 43:274–285, 2003) of 134 renal cell cancer cases (20 cases exposed to trichloroethylene) and 401 matched controls. Genetic polymorphisms of GSTT1, GSTM1, GSTP1 and NAT2 were studied. Additional control collectives of non-diseased persons were used for comparison of allele frequencies.

Results

No genetic influences on the development of renal cancer due to trichloroethylene were apparent, related to the deletion polymorphisms of GSTT1 and GSTM1, as well as to the NAT2 rapid/slow acetylator states. However, renal cell cancer cases displayed a somewhat higher proportion of the homozygous GSTP1 313A wild type (GSTP1*A), although this was not statistically significant (χ2 test: P = 0.1071, when using only the original controls of Brüning et al. (2003); P = 0.0781 with inclusion of the additional controls).

Conclusion

The re-investigation does not confirm the working hypothesis of an influence of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 on renal cell cancer development due to high occupational exposures to trichloroethylene.

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Acknowledgments

The authors thank the Deutsche Forschungsgemeinschaft (SFB 475 of the University of Dortmund, project # C7) for financial assistance.

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Authors and Affiliations

  1. Institut für Arbeitsphysiologie an der Universität Dortmund (IfADo), Ardeystr. 67, 44139, Dortmund, Germany

    Bernd Wiesenhütter, Silvia Selinski, Klaus Golka & Hermann M. Bolt

  2. Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin der Ruhr-Universität Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Dortmund, Germany

    Bernd Wiesenhütter & Thomas Brüning

  3. Fachbereich Statistik der Universität Dortmund, 44221, Dortmund, Germany

    Silvia Selinski

Authors
  1. Bernd Wiesenhütter
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  2. Silvia Selinski
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  3. Klaus Golka
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  4. Thomas Brüning
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  5. Hermann M. Bolt
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Corresponding author

Correspondence to Hermann M. Bolt.

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Wiesenhütter, B., Selinski, S., Golka, K. et al. Re-assessment of the influence of polymorphisms of phase-II metabolic enzymes on renal cell cancer risk of trichloroethylene-exposed workers. Int Arch Occup Environ Health 81, 247–251 (2007). https://doi.org/10.1007/s00420-007-0200-5

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  • DOI: https://doi.org/10.1007/s00420-007-0200-5

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