Impact of CYP2E1 genotype in renal cell and urothelial cancer patients.
Genetic polymorphisms of 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 study, we investigated the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients from two German regions, Jena and Halle, different with respect to their environmental pollution degree in comparison with healthy controls from the same regions. DNA of peripheral white blood cells was isolated both from 224 renal cell/urothelial cancer patients and 304 controls. We focussed on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphisms were identified as RFLP's by amplification of the appropriate DNA fragment and subsequent digestion with the restriction enzymes PstI, RsaI and DraI. In Jena as well as in 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. 86.2% of all subjects with a homozygote PstI/RsaI genotype also carried a heterozygote DraI genotype, whereas 5.1% of the subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. Renal cell cancer as well as urothelial cancer risk was not elevated in patients with heterozygote DraI, PstI/RsaI and combined DraI + PstI/RsaI genotypes (odds ratios slightly insignificantly increased). Interestingly enough, an association between these polymorphisms and renal cell cancer risk was found in the female subgroup but not in the male subgroup. The basis of these sex-specifically increased risks are different frequencies concerning heterozygote and homozygote genotypes in controls and cancer patients. In controls, the heterozygote genotype frequency was lower in females than in males. In renal cell cancer patients, the results were quite the contrary. Summing up, our results demonstrate an lack between CYP2E1 genetic polymorphism and renal cell/urothelial cancer risk.
Institute of Clinical Pharmacology, Friedrich Schiller University Jena, Germany.
K
K
Farker
M H
MH
Lehmann
B
B
Oelschlägel
J
J
Haerting
A
A
Hoffmann
V
V
Janitzky
J
J
Schubert
D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm; D019392:Cytochrome P-450 CYP2E1