IMPACT OF CYP2E1 GENOTYPE IN RENAL-CELL AND UROTHELIAL CANCER-PATIENTS

Genetic polymorphisms of enzymes involved in carcinogen metabolism hav e been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabol izes several drugs, precarcinogens and solvents to reactive metabolite s. In the present study, we investigated the cytochrome P450 2E1 genet ic polymorphism in renal cell/urothelial cancer patients from two Germ an regions, Jena and Halle, different with respect to their environmen tal pollution degree in comparison with healthy controls from the same regions. DNA of peripheral white blood cells was isolated both from 2 24 renal cell/urothelial cancer patients and 304 controls. We focussed on polymorphisms in the promoter region and intron 6 of the CYP2E1 ge ne. The polymorphisms were identified as RFLP's by amplification of th e appropriate DNA fragment and subsequent digestion with the restricti on enzymes PstI, RsaI and DraI. In Jena as well as in Halle, the frequ ency distributions of the PstI/RsaI, DraI and combined DraI + PstI/ Rs aI genotypes showed no significant differences between controls and re nal cell/urothelial cancer patients. We did not find significant diffe rences between Jena and Halle. 86.2% of all subjects with a homocygote PstI/RsaI genotype also carried a heterozygote DraI genotype, whereas 5.1% of the subjects with a heterocygote PstI/RsaI genotype also carr ied a heterozygote DraI genotype. Renal cell cancer as well as urothel ial cancer risk was nor. elevated in patients with heterozygote DraI, PstI/RsaI and combined DraI + PstI/RsaI genotypes (odds ratios slightl y insignificantly increased). Interestingly enough, an association bet ween these polymorphisms and renal cell cancer risk was found in the f emale subgroup but not in the male subgroup. The basis of these sex-sp ecifically increased risks are different frequencies concerning hetero zygote and homozygote genotypes in controls and cancer patients. In co ntrols, the heterozygote genotype frequency was lower in females than in males. In renal cell cancer patients, the results were quite the co ntrary. Summing up, our results demonstrate an lack between CYP2E1 gen etic polymorphism and renal cell/urothelial cancer risk.