Individual risk of toxicity or
cancer can be affected by one's exposure to sufficiently high doses of particular environmental agents (or mixtures), combined with each person's underlying
genetic predisposition. The development of unequivocal
DNA tests for
genetic susceptibility to toxicity and
cancer and the identification of individuals at increased risk, would revolutionize the fields of public health and preventive medicine. A growing number of human genetic polymorphisms in
drug-metabolizing
enzymes (
DMEs) and the receptors controlling DME expression, are being characterized, some of these have been shown to be correlated with risk of toxicity or
cancer, whereas, others presently remain equivocal and require further study. 'Phase I'
DMEs, many of which represent
cytochromes P450, sometimes metabolically activate pro-
carcinogens to genotoxic electrophilic intermediates and other times are involved in detoxification. 'Phase II'
DMEs are sometimes activating, but usually they conjugate Phase I intermediates to water-soluble derivatives, to complete the detoxification cycle. Genetic differences in the regulation, expression and activity of genes coding for Phase I and Phase II
DMEs and DME receptors that control DME activity levels, can be crucial factors in defining
cancer susceptibility and the toxic or carcinogenic power of environmental chemicals. In this review, our current knowledge about polymorphisms in several of these genes is summarized.