Genetic epidemiology of environmental toxicity and cancer susceptibility: human allelic polymorphisms in drug-metabolizing enzyme genes, their functional importance, and nomenclature issues.
Pharmacogenetics is the study of idiosyncratic drug responses that have an hereditary basis and usually reflect differences in drug-metabolizing enzymes (DMEs) and the receptors that control DME levels. The purpose of this review is to provide a brief overview of recent findings concerning more than a dozen clinically important polymorphisms and to emphasize the need to standardize the nomenclature of these alleles in each polymorphism, as quickly as possible. This nomenclature system should be consistent with the Human Gene Nomenclature Guidelines. Because DMEs have existed before divergence of prokaryotes and eukaryotes more than 2 billion years ago, it is clear that DME genes first must have evolved for critical life functions and that, more recently in animals, DME genes expanded to include the role of detoxification of dietary products, evolving plant metabolites, and, of course, pharmaceutical drugs. Many human DME polymorphisms are relevant to clinical problems in that they represent the basis of risk factors in the development of cancer, toxicity, and other diseases associated with drug, chemical, or dietary exposure. The study of the relationship among human genetic polymorphisms, cancer susceptibility, toxicity, and environmental exposure is a new and exciting area of research--which will undoubtedly have increasingly important implications for risk assessment and the prevention, early diagnosis, and intervention of clinical disease.
Nebert
D W
DW
Center for Environmental Genetics, University of Cincinnati Medical Center, Ohio 45267-0056, USA. dan.nebert@uc.edu
Ingelman-Sundberg
M
M
Daly
A K
AK
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011110:Polymorphism, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D009626:Terminology as Topic
D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System