ETHNIC VARIATION IN THE CYP2E1 GENE - POLYMORPHISM ANALYSIS OF 695 AFRICAN-AMERICANS, EUROPEAN-AMERICANS AND TAIWANESE

Human cytochrome P4502E1 (CYP2E1) is inducible by ethanol and is invol ved in metabolism of many known carcinogens including N-nitrosodimethy lamine, butadiene, benzene, and carbon tetrachloride. A 50-fold variab ility in CYP2E1 enzyme activity in humans has been observed but it is unknown whether the basis for this variation is genetic or environment al. Recently, two restriction fragment length polymorphisms (RFLPs) wi thin the CYP2E1 gene have been suggested as genetic markers of risk fo r cancer. The first was a Rsa I polymorphism in the 5' regulatory regi on that appeared to alter transcriptional activation of the gene and t he second was a Dra I polymorphism located similar to 7000 bp downstre am in an intron. Rare alleles at each of these loci have been associat ed with a reduced risk for lung cancer in Japanese and Swedish populat ions. We have used a polymerase chain reaction-restriction fragment le ngth polymorphism (PCR-RFLP) method to determine the genotype frequenc y for each of these CYP2E1 RFLPs in 695 individuals of Taiwanese, Afri can-American or European-American background. Genotype and allele freq uencies for Taiwanese were significantly different from those of Afric an-Americans and European-Americans at either Rsa I or Dra I sites (p < 0.0001). Allele frequencies for African-Americans and European-Ameri cans were significantly different at the Rsa I site (P = 0.03). The ra re alleles (c2 and C) occurred at frequencies of 0.28 and 0.24 in Taiw anese, 0.01 and 0.08 in African-Americans, and 0.04 and 0.11 in Europe an-Americans. In addition, we describe three haplotypes common to all three population samples and a fourth haplotype that was only detected in the Taiwanese population sample. This fourth haplotype may have be en caused by a recombination event between these markers. If cancer su sceptibility is modulated by the CYP2E1 DNA sequence variants we have described, then the presence of ethnic allele frequency differences su ggests the possibility of differential susceptibility to environmental ly caused cancer.