CYP2E1 genotyping in renal cell/urothelial cancer patients in comparison with control populations.
OBJECTIVE
Genetic polymorphisms in enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several drugs, precarcinogens, and solvents to reactive metabolites. In the present investigation, we studied the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients in comparison with healthy control populations in the regions of Jena and Halle in Germany.


METHODS
DNA of peripheral white blood cells was isolated both from 273 renal cell/urothelial cancer patients and 298 controls from the regions of Jena and Halle.


METHODS
We focused on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphims were identified as restriction fragment length polymorphisms (RFLPs) by polymerase chain reaction (PCR) and subsequently applying the restriction enzymes PstI/RsaI and DraI.


RESULTS
In the region of Jena as well as of Halle, the frequency distributions of the PstI/RsaI, DraI, and combined DraI + PstI/RsaI genotypes showed no significant differences between controls and renal cell/urothelial cancer patients. We did not find significant differences between Jena and Halle. 86.7% of all subjects with a homozygote PstI/RsaI genotype also carried a homozygote DraI genotype, whereas 5.2% of all subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. The heterozygote genotype of PstI/RsaI polymorphism always determines the heterozygote genotype of DraI polymorphism. Our results failed to demonstrate any differences in the distribution of CYP2E1 polymorphisms between renal cell/urothelial cancer patients and controls.


CONCLUSIONS
Summing up, our results show that CYP2E1 genotype cannot predict risk for renal cell/urothelial cancer in the population from 2 different regions in Germany. The results demonstrate a lack of association between CYP2E1 genetic polymorphism and renal cell cancer/urothelial cancer.
Farker
K
K
Institute of Clinical Pharmacology, Friedrich Schiller University, Jena, Germany.
Lehmann
M H
MH
Kästner
R
R
Hoffmann
A
A
Janitzky
V
V
Schubert
J
J
Matz
U
U
Hofmann
W
W
D002292:Carcinoma, Renal Cell / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014571:Urologic Neoplasms / Q000235:genetics*; D019459:Urothelium
D019392:Cytochrome P-450 CYP2E1