Petersen D D, McKinney C E, Ikeya K, Smith H H, Bale A E, McBride O W, Nebert D W
Laboratory of Developmental Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda.
Am J Hum Genet. 1991 Apr;48(4):720-5.
The human CYP1A1 (cytochrome P1450) gene encodes an enzyme involved in the activation of procarcinogens, such as benzo[a]pyrene, to the ultimate reactive intermediate. Approximately 10% of the human population exhibit high CYP1A1 inducibility, and Kouri et al. reported that the high-inducibility phenotype might be at greater risk than low-inducibility individuals for cigarette smoke-induced bronchogenic carcinoma. In one 3-generation family of 15 individuals, we show here that the high-CYP1A1-inducibility phenotype segregates concordantly with an infrequent polymorphic site located 450 bases downstream from the CYP1A1 gene. Our findings are consistent with the study of Kawajiri et al., who demonstrated an association between this polymorphism and an increased incidence of squamous-cell lung cancer. Our data suggest that the CYP1A1 structural gene, or a region near this gene, might be correlated with the inducibility phenotype.
人类细胞色素P1450 1A1（CYP1A1）基因编码一种参与将前致癌物（如苯并[a]芘）激活为最终反应性中间体的酶。大约10%的人群表现出CYP1A1高诱导性，Kouri等人报告称，与低诱导性个体相比，高诱导性表型个体患香烟烟雾诱导的支气管源性癌的风险可能更高。在一个由15人组成的三代家庭中，我们在此表明，CYP1A1高诱导性表型与位于CYP1A1基因下游450个碱基处的一个罕见多态性位点呈一致分离。我们的发现与Kawajiri等人的研究一致，他们证明了这种多态性与鳞状细胞肺癌发病率增加之间的关联。我们的数据表明，CYP1A1结构基因或该基因附近的一个区域可能与诱导性表型相关。
