Racial differences in restriction fragment length polymorphisms and messenger RNA inducibility of the human CYP1A1...

Recent studies have examined the relationship between genetic polymorphisms of the human cytochrome P-4501A1 (CYP1A1) gene and lung cancer susceptibility. We have quantified genotypic frequencies and measured gene expression in the CYP1A1 gene within racially diverse groups in order to determine the relationship between genotype and transcriptional regulation of the CYP1A1 gene. Lymphocytes were obtained from 68 individuals of European-American, African-American, and Asian descent, and CYP1A1 gene inducibility was measured in mitogen-stimulated cells. CYP1A1 gene inducibility was significantly lower in African-Americans than in European-Americans or Asians, while several other population parameters were found to have no effect on gene expression levels. Restriction fragment length polymorphism analysis of lymphocyte DNA following MspI restriction enzyme digestion revealed a significant difference in the frequencies of CYP1A1 genotypes between European-Americans and Asians. The only homozygous variants detected were of Asian descent. The frequencies of CYP1A1 genotypes in all races conformed to Hardy-Weinberg genotypic equilibrium. When CYP1A1 gene inducibility was compared to CYP1A1 genotype, no significant correlations were found. These studies, along with our previous survey of CYP1A1 gene expression in creosote-exposed workers, add further support to the use of CYP1A1 gene inducibility as a potential marker of polycyclic aromatic hydrocarbon exposure in human populations.