Re-assessment of the influence of polymorphisms of phase-II metabolic enzymes on renal cell cancer risk of trichloroethylene-exposed workers.
OBJECTIVE
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 (chi(2) test: P=0.1071, when using only the original controls of Brüning et al. (2003); P=0.0781 with inclusion of the additional controls).


CONCLUSIONS
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.
Wiesenhütter
Bernd
B
Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Selinski
Silvia
S
Golka
Klaus
K
Brüning
Thomas
T
Bolt
Hermann M
HM
D020022:Genetic Predisposition to Disease; D005858:Germany; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics; D016273:Occupational Exposure; D011110:Polymorphism, Genetic / Q000235:genetics*; D018570:Risk Assessment; D014241:Trichloroethylene / Q000009:adverse effects / Q000494:pharmacology*
D005982:Glutathione Transferase; D014241:Trichloroethylene; C413545:glutathione S-transferase T1