Cosma G, Crofts F, Currie D, Wirgin I, Toniolo P, Garte S J
Nelson Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Cancer Epidemiol Biomarkers Prev. 1993 Jan-Feb;2(1):53-7.
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.
最近的研究探讨了人类细胞色素P - 4501A1（CYP1A1）基因的遗传多态性与肺癌易感性之间的关系。我们对不同种族群体的CYP1A1基因的基因型频率进行了量化，并测量了该基因的表达，以确定基因型与CYP1A1基因转录调控之间的关系。从68名欧美裔、非裔美国人和亚裔个体中获取淋巴细胞，并在有丝分裂原刺激的细胞中测量CYP1A1基因的诱导性。非裔美国人的CYP1A1基因诱导性显著低于欧美裔或亚裔，而其他几个群体参数对基因表达水平没有影响。用MspI限制性内切酶消化淋巴细胞DNA后的限制性片段长度多态性分析显示，欧美裔和亚裔之间CYP1A1基因型频率存在显著差异。检测到的唯一纯合变异体来自亚洲血统。所有种族的CYP1A1基因型频率均符合哈迪-温伯格基因型平衡。当比较CYP1A1基因诱导性与CYP1A1基因型时，未发现显著相关性。这些研究，连同我们之前对接触杂酚油工人的CYP1A1基因表达的调查，进一步支持将CYP1A1基因诱导性用作人群中多环芳烃暴露的潜在标志物。
