CYTOCHROME P4502E1 GENETIC POLYMORPHISMS AND RISK OF NASOPHARYNGEAL CARCINOMA - RESULTS FROM A CASE-CONTROL STUDY CONDUCTED IN TAIWAN

CYP2E1 is responsible for the metabolic activation of nitrosamines bel ieved to be involved in the pathogenesis of various tumors, Nasopharyn geal carcinoma (NPC) is a tumor thought to be linked to nitrosamine ex posure, To investigate the possible role of CYP2E1 genetic polymorphis ms in the etiology of this tumor, we investigated 50 histologically co nfirmed NPC cases from Taiwan and 50 controls matched to cases on age, sex, and residence. Samples were examined for RFLPs in the CYP2E1 gen e by PCR amplification followed by digestion with DraI and RsaI, Among healthy controls, the allelic frequency of wild-type and variant form s of CYP2E1 were 79 and 21%, respectively, using DraI enzyme digestion and 82 and 18%, respectively, using RsaI enzyme digestion, As compare d with individuals who were homozygous for the mild-type CYP2E1 gene, those found to be homozygous for the variant form of the gene by DraI digestion were at a 5-fold excess risk of disease (95% confidence inte rval = 0.95-16), Similarly, subjects homozygous for the variant form o f the CYP2E1 gene by RsaI digestion were at 7.7-fold excess risk of de veloping NPC (95% confidence interval = 0.87-68), Individuals found to be heterozygous for the gene were at similar risk of disease compared to those homozygous for the wild-type gene, A strong association was observed between the RFLPs detected by DraI and RsaI digestion of CYP2 E1; a correlation coefficient of 0.86 for controls and 0.91 for cases was observed. Interestingly, all individuals with the variant form of CYPZE1 detected by RsaI enzyme digestion also exhibited the variant fo rm of the gene using DraI enzyme digestion, although the reverse was n ot always true, Our results confirm previous findings suggesting that the distribution of CYP genotypes among Oriental populations varies fr om that observed among Caucasians and demonstrate for the first time a possible association between CYP2E1 genetic polymorphisms and the ris k of developing NPC.