CYP2E1 GENOTYPING IN RENAL-CELL UROTHELIAL CANCER-PATIENTS IN COMPARISON WITH CONTROL POPULATIONS

Objective: Genetic polymorphisms in enzymes involved in carcinogen met abolism 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 reactiv e metabolites. In the present investigation, we studied the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patient s in comparison with healthy control populations in the regions of Jen a and Halle in Germany. Patients and material: DNA of peripheral white blood cells was isolated both from 273 renal cell/urothelial cancer p atients and 298 controls from the regions of Jena and Halle. Method: W e 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 su bsequently applying the restriction enzymes PstI/RsaI and DraI, Result s: In the region of Jena as well as of Halle, the frequency distributi ons of the PstI/RsaI, DraI, and combined DraI + PstI/RsaI genotypes sh owed no significant differences between controls and renal cell/urothe lial cancer patients. We did not find significant differences between Jena and Halle, 86.7% of all subjects with a homocygote PstI/RsaI geno type also carried a homocygote DraI genotype, whereas 5.2% of all subj ects with a heterocygote PstI/RsaI genotype also carried a heterocygot e DraI genotype. The heterocygote genotype of PstI/RsaI polymorphism a lways determines the heterocygote genotype of DraI polymorphism. Our r esults failed to demonstrate any differences in the distribution of CY P2E1 polymorphisms between renal cell/urothelial cancer patients and c ontrols. Conclusion: Summing up, our results show that CYP2E1 genotype cannot predict risk for renal cell/urothelial cancer in the populatio n from 2 different regions in Germany. The results demonstrate a lack of association between CYP2E1 genetic polymorphism and renal cell canc er/urothelial cancer.