ROLE OF GENETICS AND DRUG-METABOLISM IN HUMAN CANCER RISK
ROLE OF GENETICS AND DRUG-METABOLISM IN HUMAN CANCER RISK
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DOI：
10.1016/0027-5107(91)90022-g
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发表时间：
1991-04-01
期刊：
影响因子：
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通讯作者：
NEBERT, DW
中科院分区：
文献类型：
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作者：
NEBERT, DW
关于药物反应具有遗传基础的研究领域被称为“药物遗传学”。 在临床医学中，至少有50多个药物遗传学多态性被描述;许多是导致毒性或癌症遗传易感性显著差异的原因。 这里详细介绍了三种：乙酰化、异喹胍和AH位点多态性。 所有这三种在美国人群中都很常见：2人中有1人是“慢乙酰化者”，12人中有1人是异喹胍组中20多种常用处方药的“弱代谢者”，10名患者中有1名患者的CYP 1A 1和CYP 1A 2（细胞色素P（1）450和P（3）450）基因高度可由香烟烟雾诱导。 同一家族中的个体之间异源生物质代谢的差异可能超过200倍，这表明职业危险化学品以及具有狭窄治疗窗口的处方药可能会在不同基因型的患者之间引起显著不同的影响。 我们的最终目标是“预防毒理学”，即开发简单，廉价，明确和敏感的检测方法来预测毒性或癌症的个体风险。 这些测试可以帮助个人选择更安全的生活方式或工作场所，并可能帮助医生决定开哪种药物。
The research field concerning responses to drugs having a hereditary basis is called 'pharmacogenetics'. At least 5 dozen pharmacogenetic polymorphisms have been described in clinical medicine; many are responsible for marked differences in genetic predisposition toward toxicity or cancer. Three are detailed here: the acetylation, the debrisoquine, and the AH locus polymorphism. All 3 are very common among the United States' population: 1 in 2 is a 'slow acetylator', 1 in 12 is a 'poor metabolizer' for more than 2 dozen commonly prescribed drugs in the debrisoquine panel, and the CYP1A1 and CYP1A2 (cytochromes P(1)450 and P(3)450) genes are highly inducible by cigarette smoke in 1 of 10 patients. Differences in xenobiotic metabolism between individuals in the same family can be greater than 200-fold, suggesting that occupationally hazardous chemicals, as well as prescribed drugs having a narrow therapeutic window, might cause strikingly dissimilar effects between patients of differing genotypes. Our ultimate goal is 'preventive toxicology', i.e. the development of simple, inexpensive, unequivocal and sensitive assays to predict individual risk of toxicity or cancer. These tests could help the individual in choosing a safer life style or place of work and might aid the physician in deciding which drug to prescribe.