Idle J R, Daly A K
Department of Pharmacological Sciences, Medical School, Newcastle upon Tyne, UK.
Environ Health Perspect. 1993 Oct;101 Suppl 3(Suppl 3):117-20. doi: 10.1289/ehp.93101s3117.
Genetic polymorphisms of drug-metabolizing enzymes, principally CYP2D6 (debrisoquine 4-hydroxylase), have long been considered influential on host responsiveness to environmental carcinogens. In several independent studies, lung cancer cases are more frequently associated with the extensive metabolizer phenotype of CYP2D6. However, assignment of phenotype has traditionally involved administration of debrisoquine and analysis of drug and metabolite concentrations in patient urine and is thus potentially confounded by concomitant drug therapy and the presence of the tumor itself. The development of molecular genotyping methods offers unique opportunities to obviate these problems and to ascertain the relationship between the presence of individual alleles and disease risk. Preliminary data are presented that indicate that the CYP2D6 wild-type allele may be a predisposing factor in lung cancer.
药物代谢酶的基因多态性，主要是细胞色素P450 2D6（异喹胍4-羟化酶），长期以来一直被认为对宿主对环境致癌物的反应性有影响。在几项独立研究中，肺癌病例更常与细胞色素P450 2D6的广泛代谢者表型相关。然而，传统上确定表型的方法涉及给予异喹胍并分析患者尿液中的药物和代谢物浓度，因此可能会受到同时进行的药物治疗和肿瘤本身存在的干扰。分子基因分型方法的发展为消除这些问题以及确定个体等位基因的存在与疾病风险之间的关系提供了独特的机会。本文给出的初步数据表明，细胞色素P450 2D6野生型等位基因可能是肺癌的一个易感因素。
